ECM Flashcards
1
Q
What are the two major fibers in the ECM?
A
collagen & elastin
2
Q
Basal lamina is a special type of ____
A
ECM
3
Q
Anything below basal lamina is the:
A
Dermis
4
Q
What are embedded in the proteoglycan gel?
A
fibers
5
Q
What does fibronectin bind to?
A
integrin & collagen
6
Q
What is the function of collagen?
A
strengthens, resists stretching, organizes ECM
7
Q
What is the function of elastin?
A
elasticity
8
Q
What is fibrillin?
A
a protein required for assembly of elastic fibers
9
Q
What is the function of fibrillin?
A
forms a protein coat around elastic fibers, its required for assembly of elastic fibers
10
Q
Besides collagen and elastin, what major substance is in the ECM?
A
Ground substance
11
Q
What is the function of ground substance?
A
hydrated gel, resists compressive forces, permits rapid diffusion of nutrients, metabolites & hormones between blood & tissue
12
Q
What two major substances are found in ground substance?
A
proteoglycans
glycoproteins
13
Q
What composes proteoglycans?
A
Mostly GAGs and a little protein
14
Q
What is the function of proteoglycans?
A
resist compression & fill spaces
15
Q
What composes glycoproteins?
A
Mostly protein, a little GAGs
16
Q
What is the function of glycoproteins?
A
Adhesive glycoproteins
17
Q
What are three major glycoproteins in ECM?
A
fibronectin, laminin, entactin
18
Q
Corneal & stroma ECM is transparent - why?
A
fibers are arranged in parallel bundles
19
Q
How is ECM arranged in bone & teeth? (very generally)
A
its calcified
20
Q
How is ECM arranged in tendons? (very generally)
A
ropelike
21
Q
How is ECM arranged in cartilage? (very generally)
A
lots of collagen with ground substance - to absorb shock
22
Q
Name the 5 functions of fibrous proteins
A
Fibrous proteins have physical properties that impart strength or flexibility
Simple repeating element of secondary structure
Water insoluble (hydrophobic residues packed in center)
Extracellular, long-lived proteins
Used to construct connective tissue, tendons, bone matrix
23
Q
Collagen is what percentage of our proteins?
A
25%
24
Q
What is the structure of collagen?
A
Thee collagen alpha chains wind together to form a triple helix
25
How is collagen arranged in skin?
loosely woven, arranged in all directions for support no matter which way skin is pulled
26
Every third aa of the alpha chain that makes collagen is made of what?
glycine
27
Why is it important that glycine is arranged every 3rd aa in alpha chain for collagen?
allows tightly packed triple helix (glycine is small), allows for hydrogen bonding w/ adjacent helix
28
How is collagen arranged in tendons?
parallel bundles
29
What cell makes collagen?
fibroblasts & epithelial cells
30
What is the only type of collagen found in basal lamina?
Type IV
31
Besides glycine, what aa is found on alpha helix of collagen?
proline & lysine
32
What often happens to the proline and lysine on the aa of alpha chain of collagen?
it is hydroxylated
33
Why is there hydroxyproline & hydroxylysine on alpha helix of collagen?
allows more hydrogen bonds b/w alpha chains, more stability
34
What is significant about the triple helix structure of collagen?
like cables of suspension bridge, very strong, resists unwinding
35
What is preprocollagen?
alpha chain (collagen) with ER signal sequence with propeptide domain at C & N terminus
36
What is the name of the alpha chain that will become collagen before it enters the ER?
preprocollagen
37
What does the "pre" mean in preprocollagen
it has an N terminal signal sequence to direct it to the rER for synthesis
38
What does preprocollagen become?
procollagen
39
What takes off the ER signal sequence from the preprocollagen?
signal peptidase
40
Type I collagen has how many alpha 1 chains and how many alpha 2 chains?
2 alpha 1 chains
| 1 alpha 2 chain
41
What does the "pro" mean in procollagen?
peptide domains @ C & N terminus
42
Three procollagen alpha chains assemble together to form a triple helix, where does this occur?
ER
43
Where do disulfide bonds form on propeptides?
C terminus
44
Where and when are propeptide domains cleaved off of procollagen?
Propeptide will be joined in ER, then go to golgi, then excreted into ECM. then the propeptide domain will be cleaved off.
45
Where are collagen fibers formed?
In ECM after propeptide domain cleaved, they will spontaneously join and form large fibers
46
What is the function of the propeptide domain on procollagen?
prevents associtaion of collagen fibril forming inside cell (its too big for cell!), helps form helix
47
What happens to some hydroxylysines inside the ER?
they are glycosylated
48
Where are disulfide bonds formed on procollagen in ER?
C terminus
49
What is the function of the disulfide bonds in procollagen?
helps align the alpha chains, initiates triple helix formation, kind of acts like a zipper to bind the helixes
50
The disulfide bonds have what's called a "zipper mechanism" where they help join alpha chains to form helix - describe the zipper mechanism
"zips" up the three chains starting at C terminus and going to N terminus
51
Hydroxyproline is only found in what two places?
Collagen & elastin
52
The enzymes that convert proline and lysine to hydroxyproline & hydroxylysine require what?
ascorbic acid (vitamin C) and iron
53
What is ascorbic acid?
Vitamin C
54
What are the three enzymes we need to know that convert proline & lysine to hydroxyproline & hydroxylysine?
Prolyl-3-hydroxylase
Prolyl-4-hydroxylase
Lysyl hydroxylase
55
What happens if there is a lack of hydroxyproline?
decreased stability of triple helix in collagen
56
What happens if there is no hydroxyproline in collagen?
collagen loses almost all of its helical content
57
Key words: anemia, fatigue, bleeding gums is what disease?
scurvy
58
Characteristics: Bleeding gums, loosened teeth, petechiae (pinpoint hemorrhages around air follicles, gums, nails); ecchymoses, poor wound healing, poor bone development, anemia & fatigue are what disease?
Scurvy
59
What is the mechanism for scurvy?
Vit C is required for hydroxylationof proline & lysine; deficiency of Vit C → lack of hydroxyproline → no H bonds → decreased stability of collagen triple helix → weak CT
60
What is the mode of inheritance for scurvy?
Acquired
61
Where is the defect in scurvy?
Vitamin C (ascorbic acid) deficiency; unstable collagen
62
How long does it take for a person not eating any vitamin C to see symptoms of scurvy and why?
20-40 days, remodeling of CT takes time
63
What removes the propeptides on procollagen once it is excreted into the ECM?
peptidases
64
Why do propeptides need to be removed from collagen?
so that the collagen can form add'l bonds and cross link
65
What kind of interactions stabilize the collagen fibrils?
covalent
66
What aa is often on the end of collagen?
lysine
67
Lysines (and hydroxylysines) convert into what on collagen?
aldehydes
68
What converts lysines (and hydroxylysines) into aldehyde?
lysyl oxidase
69
Why are lysines converted to aldehydes?
So they can covalently bond to other collagen fibers
70
What is the function of aldehydes on collagen fibers?
Aldehydes react spontaneously
→ covalent bonds with each other or other lysines or hydroxylysines
Usually at ends
Stabilise side-by-side packing
71
What are the different types of fibrillar collagen?
Type I, II, III, V
72
What are the different types of FACIT collagen?
Type VI, IX, XII
73
What does FACIT stand for?
Fibril-Associated Collagens (VI, IX, XII) with Interrupted Triple helices
74
What are the different types of sheet (networking)-forming collagen?
Type IV, X
75
What are the different types of anchoring fibrils?
VII
76
Type I, II, III, V belong to which collagen family?
Fibrillar
77
What type of collagen is the only one found in the basal lamina?
Type IV (Sheet-forming collagen)
78
Where are anchoring fibrils found?
They anchor the basal lamina to the interstitial matrix
79
Type VI collagen binds and links what type of fibril?
Type I
80
Type IX collagen binds and links what?
bind & link type II fibrils & bind chondroitin sulfate (GAG)
81
Key words: hyperextensible skin, hypermobile joints, fibrillar collagen is what disease?
Ehlers-Danlos Syndrome
82
Characteristics: Hyperextensible fragile skin, joint hypermobility & dislocations is what disease?
Ehlers-Danlos Syndrome
83
What is the mechanism for Ehlers-Danlos Syndrome?
Defected fibrillar collagen synthesis → improper assembly of collagen → connective tissue weakness
84
Where is the defect in Ehlers-Danlos syndrome?
Defected collagen (fibrillar collagen – I, III, V) synthesis
85
What coats the surface of fibrillin collagen and helps them bind together and to other components?
FACIT
86
____ is more flexible than fibrillar colalgen
FACIT
87
After it is secreted, what part of ECM retains its propeptides?
FACIT
88
Describe the structure of FACIT
3 stranded structure interrupted by non-helical domains, the non-helical domains cause kink
89
What two enzymes allow for the degradation of collagen?
MMP-1 & MMP-2
90
Why is it important to have enzymes to degrade the collagen in ECM
for remodeling, to help cells move, to help heal
91
What does MMP stand for?
Matrix Metalloproteinases
92
What is another name for MMP-1?
Collagenase I
93
What is another name for MMP-2?
Collagenase IV
94
What does MMP-2 degrade?
Type IV collagen → basal lamina
95
What type of cell is MMP-2 overexpressed
cancer cells (esp. epithelial cancer)
96
How are MMPs present in the ECM?
they are zymogens
97
What is a zymogen
Inactive enzyme
98
How does the body activate the MMPs that are inactive zymogens?
cleaved and activated
99
MMP can be stored where?
ECM
100
What is an inhibitor of MMP?
TIMPs
101
What is the dominant ECM protein in arteries?
elastin
102
What tissues have a lot of elastin?
arteries, skin, lungs, uterus
103
What amino acids are often in elastin?
glycine & proline
104
Collagen has glycine and proline like elastin - what is the difference in terms of these aa in elasin?
they will not be glycosylated and there is no hydroxylysine
105
Collagen fibers are often interwoven with what to prevent tearing and limit stretching?
elastic fibers
106
How is elastic tissue in relaxed state attached? (aka what type of bond)
covalently
107
tropoelastin molecules spontaneously assemble to form what?
elastic tissue
108
What is the main glycoprotein that covers elastin core?
fibrillin
109
If there is a mutation in fibrillin what is the disease?
marfan syndrome
110
What does fibrillin bind to?
elastin
111
what forms a scaffold for deposited elastin?
microfibrils
112
What is fibrillin essential for?
assembly & integrity of elastic fibers
113
Characteristics: Aortic root dilation & dissection, lens subluxation & retinal detachment, tall & thin, long limbs & fingers – archnodactylyl, funnel chest – pectus excavatum is what disease?
Marfan syndrome
114
What is the mechanism for marfan syndrome?
Defect in fibrillin → weak elastic tissue
115
What is the mode of inheritance for marfan syndrome?
AD
116
Where is the defect for marfan syndrome?
Defect in fibrillin (elastin)
117
What can happen to the aorta in a person who has marfan syndrome?
blood going through aorta with high pressure, can rupture part of wall and create false lumen
118
What does arachnodactyly mean?
long limbs & fingers
119
What does pectus excavatum mean?
funnel chest
120
What enzymes allows degradation of elastin?
elastase
121
Lungs inhibit what enzyme so there is no degeneration of its elasticity?
elastase
122
Why do the lungs need to inhibit elastase?
they cannot regenerate
123
What is the name of a serine protease secreted by neutrophils?
elastase
124
why do WBC need to secrete elastase?
so they can move through ECM
125
What is an inhibitor of elastase?
α1-antitryspin
126
α1-AT stands for what?
α1-antitryspin
127
What secretes alpha1-AT?
liver
128
key words: alpha1-AT, hyperventilation, respiratory distress, barrel chest are what disease?
emphysema/COPD
129
Characteristics: Dyspnea, hyperventilation, hyper-inflated chest (barrel chest); develop emphysema by 30-50 years old (early if smoker) are what disease?
emphysema/COPD
130
What is the mechanism for emphysema/COPD?
Deficiency of alpha1-AT → uninhibited destruction of elastic fibers by elastase → loss elastin in respiratory tissues → less flexible alveolus, stagnant alveolar air, respiratory insufficiency → respiratory distress; smoke inhibits alpha1-AT & recruits neutrophils to the lungs that released elastase (faster destruction in a smoker with deficiency) [Normally, elastase breaks down elastic fibers & it is inhibited by alpha1-antitrypsin]
131
What is the mode of inheritance for emphysema/COPD?
AR
132
Where is the defect for emphysema/COPD?
Deficiency of alpha1-antitrypsin (elastase)
133
Cigarette smoke can cause irritation and inflammation in lungs as well as inhibit what?
α1-AT
134
Describe how smoking could cause emphysema
Smoking inhibits alpha 1-AT and causes infections which promote neutrophils. Neutrophils release elastin and since there is no alpha1-AT to inhibit it, it will break down tissue. Lung tissue cannot regenerate
135
Empysema is a form of:
COPD
136
GAGs are covalently linked to a core protein to form what?
proteoglycan
137
Hyaluraun, dermatan sulfate, chondroitin sulfate, keratin sulfate, heparin (heparan sulfate) are all examples of what?
GAGs
138
What is the exception to the GAGs important esp. regarding proteoglycans
they are all sulphated except hyaluron
139
Explain the difference b/w hyaluron and the other GAGs
hyaluron is not sulfated, it can associate with proteoglycans but cannot form a proteoglycan
140
What can Hyaluronan associate with but not form?
proteoglycan
141
GAGs all have what charge
negative
142
How is the negative charge of GAGs important for the gelly like substance in ground substance?
the negative charge attracts a lot of water
143
What is the biggest GAG?
Hyaluronan
144
What is the only GAG that is made extracellularly?
Hyaluronan
145
Where is Hyaluronan synthesized?
by enzyme on basal epithelial surface
146
Why does Hyaluronan have to be synthesized extracellularly?
b/c it is too big to be made inside a cell
147
What produced during wound healing and provides backbone for cells to migrate to for the healing?
Hyaluronan
148
What is the lubricant of joint fluid? (What GAG)
Hyaluronan
149
How much of vitreous humour is water?
99%
150
How is so much of vitreous humour water?
It has a lot of proteoglycans and hyaluronan
151
Proteoglycan can form large complexes with what?
hyaluronan
152
Four sugars link GAG chain to what?
core protein
153
How are GAGs attached to core protein?
covalently attached, linked to core protein by four sugars
154
What kind of bond does hyaluronan use to bind to existing proteoglycans?
non-covalent
155
The core protein has what kind of domain to bind to hyaluronan?
n-terminal hyaluronan binding domain
156
What is aggrecan?
combination of hyaluronan assembling proteoglycans on its surface
157
How do core proteoglycans associate with hyaluronic acid?
link proteins
158
What forms the central core of aggrecan?
hyaluronic acid
159
where will lots of aggrecan be found?
cartilage - it helps resist compression
160
Describe the structure of aggrecan
a hyaluronan molecule attached to a bunch of core proteins (aggrecan) via linking proteins, there are a bunch of sulfates (like keratan sulfate & chondroitin sulfate) attached to the core protein
161
What is another name for the core protein?
aggrecan
162
Explain the function of proteoglycans as a porous hydrated gel in the ECM
Fills spaces: Occupy a large volume
| Resists compression
163
Expain the function of proteoglycans as a structural component of the ECM
Associate with eachother, collagen & basal lamina
164
Explain how proteoglycans help with cell signaling in the ECM
Bind growth factors
| Increase cell surface receptor binding affinity for the growth factors
165
Explain how proteoglycans help with cell migration in the ECM
Create cell free space
Bind & regulate activity of proteases & their inhibitors
Immobilize chemokines (during inflammation)
166
What type of collagen is found in basal lamina?
Collagen Type IV
167
Basal lamina and above in skin is what?
epidermis
168
Below basal lamina is what in skin?
dermis
169
What collagen anchors the dermis to epidermis?
Collagen Type VII
170
Components of basal lamina are secreted by what?
epithelial cells
171
Interstitial cells are secreted by what?
fibroblasts or fibroblast type cells (chondrocytes, etc)
172
What are the four components we need to know that make up the basal lamina?
Type IV collagen
Laminin
Entactin/Nidogen
HSPGs- perlecan
173
What is another name for entactin?
Nidogen
174
Basal lamina is a specialized:
ECM
175
What does HSPG stand for?
heperan sulfate proteoglycan
176
What are some specific cells the basal lamina surrounds?
skeletal muscle cells, adipocytes, schwann cells
177
What important part of the kidney does the basal lamina play a huge role?
kidney glomerulus
178
Why is the basal lamina so important in the kidney glomerulus?
forms permeability barrier, important for filtration
179
What is attached to the basal lamina that binds to laminin?
integrin receptors
180
What is an adhesive glycoprotein that attaches to cell receptors?
laminin
181
What does laminin associate with in the basal lamina?
Type IV collagen
perlecan
nidogen
182
What does type IV collagen bind to in basal lamina?
perlecan
nidogen
laminin
183
What is not cleaved off of type IV collagen? and why?
propeptide domain is not cleaved off so it wont spontaneously form fibrils
184
What is actually binding to the cells integrin receptors in basal lamina?
laminin
185
What binds to form the scaffold for basal lamina?
laminin & type IV collagen
186
What anchors the epithelial cells to the basal lamina?
laminin
187
What are the names of the cell membrane laminin receptors that laminin binds to in the basal lamina?
integrins, dystroglycan
188
What is the most prevelant part of the basal lamina?
laminin
189
Laminin receptor binding (adhesion) promotes what?
cell growth & differentiation
190
Where is perlecan found?
all basement membranes
191
What is the function of perlecan?
mediates cell attachment to basal lamina for endothelial cells & fibroblasts; it anchors proteoglycan in matrix and increases its strength
192
What does perlecan bind to specifically in basal lamina?
entactin, laminin, collagen IV & fibronectin
193
What two HSPGs function in angiogenesis & mitogenesis?
perlecan & syndecan
194
The plasma membrane of a cell has what kind of receptor that has high affinity for, for example, FGF
growth factor receptor
195
What is an example of a transmember proteoglycan?
syndecan
196
When a GAG presents a growth factor to receptor, the receptor has:
high affinity for it
197
When a growth factor receptor binds a growth factor, what happens?
signal transduction pathway
198
How can the ECM influence signal transduction?
Can present things for cell to bind to that start pathways, like growth factor
199
What do entactin & perlecan bind to?
laminin & collagen IV
200
Entactin & perlecan bind to laminin & colalgen IV in order to:
connect the 2 networks (pg 47)
201
What ECM proteins does entactin bind?
perlecan & fibronectin
202
How are GAGs an important part of the kidney glomerulus?
size-selection barrier & charge selective barrier
203
How do GAGs act as a size-selection barrier in the kidney glomerulus?
HSPG prevent macromolecules from passing into urine from blood
204
How do GAGs act as charge selective barrier in kidney glomerulus?
HSPGs give it negative charge, most proteins are neg. charged, so HSPGs repel them and don't allow them to cross
205
What happens to the kidney glomerulus in a person with diabetes?
the basal lamina becomes disorganized and doesn't filtrate properly.
206
Key words: hyperglycemia, HSPG defect, proteinuria, progressive renal failure, dialysis are what disease?
Diabetic Nephropathy: Hyperglycemia, Diabetes Mellitus
207
Characteristics: Proteinuria, fluid retention, HTN → further damage → progressive renal failure; #1 indication for dialysis are what disease?
Diabetic nephropathy: hyperglycemia, diabetes mellitus
208
What is the mechanism for diabetic nephropathy?
Hyperglycemia → downregulation of HSPG (perelcan), collagen glycosylation & crosslinking → GBM thickening: increased collagen, decreased HSPG → expansion of mesangial matric
209
Where is the defect for diabetic nephropathy?
HSPG defect (basement membrane defect)
210
Diabetic nephropathy will eventually lead to what?
Renal failure
211
Describe the 6 main functions of the basal lamina
Structural support for cells (Transmembrane integrin receptors bind to collagen IV and Laminin)
Organises cells & tissues
Scaffold for tissue regeneration
Filter (kidney glomerlus; thick BL prevents macromolecules passing from blood to urine) (Collagen IV & HSPG important)
Determines cell polarity
Influences cell survival, proliferation, differentiation
Selective barrier for cell migration
212
What will you not find in the basal lamina?
elastin & fibrillin
213
What is fibronectin?
Adhesive glycoprotein that the cells integrin receptors bind to in interstitial matrix (like fibroblasts).
214
Fibronectin ______ the ECM and helps ____ attach to it
organizes, cells
215
Fibronectin connects cells to all ECM except for what?
Type IV ECM: Basal lamina mediated by laminin
216
Fibronectin forms what?
dimers
217
The fibronectin dimer is connected by what kind of bonds?
disulphide bonds
218
Name the four binding domains of fibronectin
heparin binding
cell binding
collagen binding
self-association
219
What aa sequence is within the cell binding domain?
RGD sequence
220
The RGD sequence is found where?
on binding domain of fibronectin & laminin
221
What do integrin receptors specficially bind to on fibronectin & laminin?
RGD aa sequence
222
What is the function of the self association domain on the fibronectin?
when cells integrin receptors start binding to fibrnectins, the fibronectins will start associating toegether outsid ecell to form fibronectin fibrils
223
RGD stands for what amino acids?
arginine, glycine, asparagine
224
What binds to fibronectin?
collagen, proteoglycans, fibrin
225
What secretes fibronectin?
fibroblasts
226
fibrillar fibronectin mimics what in its formation?
the cytoskeleton of surrounding cells, and vice versa
227
Describe the orientation of fibers in fibrillar fibronectin?
arranged in same orientation
228
Fibronectin dimers _____ and assemble into fibrils by binding to integrins at cell surface
cross link
229
Whose function is: Causes cells to assume their normal shapes & grow in the right direction (aligns cytoskeleton with fibronectin fibrils)
fibronectin
230
What is a proteoglycan that helps with attachment b/w cell and ECM & helps w/ adhesion and signalling?
syndecan
231
What functions as an alpha/beta heterodimer and is the main receptor for attaching cell to the ECM?
Integrins
232
Is the bond b/w integrins and ECM strong?
No, each individual attachment is weak
233
Each individual attachment to integrin and ECM is weak, explain how they are able to attach to ECM effectively
They function like velcro- individually they are weak but together they can form a strong enough bond. This helps for movement of cells, they can detach easily.
234
What are the Principal cell receptors for binding ECM (collagen, fibrinogen, laminin)?
Integrins
235
What links the ECM with intracellular signaling?
Integrins
236
Name this anchoring junction: Integrins bind to actin stress fibers via adapter proteins, and to fibronectin
Focal adhesions
237
Name this anchoring junction: Integrins bind to intermediate filaments (keratins) via adapter proteins, and to laminin
hemidesmosomes
238
What binds to F-actin stress fibers in the cell?
adapter protein on integrin
239
What binds to keratin in cell?
adapter protein on integrin
240
What junction is very important during cell migration?
focal adhesions
241
What is the "feet" of cell during cell migration
focal adhesions
242
In focal adhesions, name the two adaptors for integrins and actin inside the cytoplasm of cell
vinculin & talin
243
What is the protein that cross links alpha stress fibers (inside cell of a focal adhesion complex)
alpha actinin
244
What kinase do integrins signal through to signal migration to cell?
FAK: focal adhesion kinase
245
Growth factor can cause changes in what kind of receptor?
integrin. what integrin receptors bind to outside cell can cause changes inside the cell
246
What is the strongest anchor b/w the cell and the ECM?
hemidesmosome
247
What is the name of the intermediate filament important in hemidesmosomes?
keratin
248
keratin inside cell are embedded into plaques containing:
plectin
249
What does plectin bind to?
IFs
250
What link the intracellular plaques to the ECM laminin in hemidesmosomes?
Integrin
251
Hemidesmosomes are anchored by what kind of collagen?
VII
252
key words: autoimmune, hemidesmosomes, blister formation ABOVE the basal lamina is what disease?
Bullous Pephigoid
253
Characterstics: Subepidermal blisters or psoriasiform pattern; onset > 60 years are what disease?
bullous pephigoid
254
What is the mechanism of bullous pephigoid?
Autoantibodies attacking hemidesmodomal protein (plectin plaques) → disrupts dermal-epidermal junction (rupturing between cell & basal lamina)
255
Where is the defect in bullous pephigoid?
Autoimmune destruction of hemidesmosome [IF: cell-matrix]
256
What disease has autoimmune destruction of hemidesmosomes?
bullous pemphigoid
257
Draw out the attachements of focal adhesions & hemidesmosomes
Pg 67 & 69
258
What 2 gene proteins are important for cell motility?
RAC & CDC42
259
What is the function of Filopodia?
sensors to be sure cell is moving in right direction during migration
260
What protein rearranges actin to stretch front out in a lamellopodium?
RAC
261
What protein mediates new focal contacts made in cell migration?
RHO
262
What G protein is important for stress fibers & focal contacts?
RHO
263
What G protein is important for lamellipodium that extends from the entire circumference of the cell?
RAC
264
What G protein is important for filopodia protrusion, form adhesive contacts with substratum ?
Cdc42
265
What is the strongest form of cell -cell adhesion?
desmosomes
266
Starting at the apical surface of the cell, name the order of appearance of cell-cell junctions
1. tight
2. adherins
3. desmosomes
4. gap
267
What is another name for tight junction?
Occluding Junction or Zonula occludens
268
What is a barrier that completely encircles the apical layer of each cell?
Tight junction
269
What transmembrane adhesion proteins help form the tight junction?
claudin & occludin
270
What kind of junction determines epithelial cell polarity?
Tight junction
271
What do they think is downregulated in inflammatory bowel disease that allows for more permeability of membrane for WBC to cause immune response?
occludin
272
Anchoring receptors and desmosomes use what family of proteins ?
cadherins
273
Cadherins are dependent on what ion?
calcium
274
What forms continuous adhesion belt (zonula adherens) in epithelia just below TJs
Adherens junctions
275
In adheren junction, the E cadherin of one cell binds to what part of adj. cell?
E. cadherin
276
How do cadherins bind to the actin cytoskeleton?
via catenins
277
If actin are cross linked by alph actinin, will they be contractile?
Yes, they are loosely packed so will be contractile
278
What is the difference b/w adherens junctions & desmosomes?
Major difference between desomosomes & adherens (belt) junctions:
Adherens junctions connect to F-actin, not IFs
Adherens junctions are near the apical surface (actin-rich region)
Form a continuous belt around cell, not spot welds
Linker proteins = catenins (important signaling molecules; GI & hepatic cancer)
279
What are the two specific intracellular anchor proteins that attach to cadherins in desmosomes?
desmoplakin & plakoglobin
280
What do desmoplakin & plakoglobin bind to?
IFs & cadherin
281
Desmoplakin & plakoglobin are both part of what that binds to IFs and are connected via cadherins?
plaques
282
key words: autoimmune, desmosomes, blistering are what disease?
Pemphigus vulgaris
283
Characteristics:Blistering & raw sores on skin & mucous membrane are what disease?
Pemphigus vulgaris
284
What is the mechanism for pemphigus vulgaris?
Antibodies attacking desmosomal proteins → skin pulls apart → abnormal movement of fluid within skin → blisters
285
What is the mode of inheritance for pemphigus vulgaris?
autoimmune disorder
286
Where is the defect in pemphigus vulgaris?
Autoimmune destruction of desmosomal cadherins(anti-desmogelin) [IF: cell-cell]
287
What connects both cytoplasms in a gap junction?
connexons
288
What forms a connexon?
6 connexin subunits
289
What cell connection allows free passage of ions, sugars, aas, nucleotides, 2nd messengers (cAMP, IP3)?
gap junctions
290
What are the two main functions of gap junctions?
electrical coupling & chemical coupling
291
The coordinated depolarisation of the heart is an example of what function of gap junctions?
electrical coupling
292
2nd messengers, like in cAMP pathway, is an example of what function of gap junctions?
chemical coupling
293
What does CMT stand for?
Charcot-Marie-Tooth
294
Briefly describe Charcot-Marie-Tooth
Name: Charcot-Marie-Tooth Neuropathy Defect: Connexin Mutation [cell-cell gap junction] Mode of Inheritance: X-linked Mechanism: Mutation of connexin 32 ! demyelination of Schwann cells ! progressive degeneration of peripheral nerve function Characteristics: Muscle weakness & atrophy, impairment of deep tendon reflexes Key words: connexin, gap junction, deep tendon reflexes
295
Selectins belong to what class of proteins?
lectins
296
What are selectins?
proteins that bind to sugar chain instead of actual protein
297
What type of selectin is expressed on WBC?
L-selectin (L = leukocyte)
298
What type of selectin is expressed on platelets?
P-selectin
299
What type of selectin is expressed on endothelial cells?
E-selectin
300
Draw out all the steps in lymphocyte rolling, and explain each part
See slide 124 in ECM & cell interactions
301
What is diapedesis?
WBC migration into tissue
302
What is the weak adhesion and what is the strong adhesion in lymphocyte rolling?
weak: selectins on endothelial cells
| strong; Integrin binds ICAM on endothelial cells
303
What happens if there is a mutation in beta2 integrin?
Inherited mutation in beta 2 integrin. Integrin are heterodimres beta 2 is one of the integrins that’s really important in leukocyte extravasation. Mutation in integrin, when there is infection will get activation of nearby endothelial cells which express selectins, leukocytes bind, but cant get tracking .if cell cant be tracked b/c integrin cant bind to ICAMS it will just keep rolling along.
ultiamtely the pt will suffer from lots of bacterial infections
304
key words: B3 integrin, glycoprotein IIb-IIa, platelet aggregation defect is what disease?
Glanzmann’s Thrombasthenia
305
Characteristics: Excess bruising and bleeding is what disease?
Glanzmann’s Thrombasthenia
306
What is the mechanism of Glanzmann’s Thrombasthenia ?
Absence of platelet integrin complex → no binding to fibrinogen → failure of platelet aggregation → defective clotting
307
Where is the defect in glanzmann's thrombasthenia?
Mutation of B3 integrin (glycoprotein IIb-IIIa)
308
List the collagen defect disorders
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Osteogenesis Imperfecta Collagen I
Ehlers-Danlos syndrome Collagen I, III, V
Alport syndrome Collagen IV
Goodpasture syndrome Collagen IV
Epidermolysis bullosa Collagen VII
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