Exam 3 pt 2 Flashcards
1
Q
epithelial cells rely
A
on cell-cell junctions
2
Q
connective tissue cells rely on
A
cell matrix junctions
3
Q
tight junctions have _ and function to _
A
no resistance to stress and prevent leaking
4
Q
intracellular domains of transmembrane adhesion linked to _ proteins are while extracellular domains are linked to
A
linked to cytoskeletal filaments, structures outside of the cell
5
Q
superfamilies of adhesion proteins
A
- integrins
- cadherins
6
Q
cadherins for _ via _
A
cell cell junctions via actin adherens junctions or intermediate filament desmosomes
7
Q
integrins form _ via
A
cell matrix junctions (to ECM) via actin linked cell matrix junctions or intermediate filament hemidesmosomes
8
Q
all cadherin family members
A
have several copeies of the extracellular adherin domain
9
Q
in cadherins, adjacent domains are linked by
A
flexible hinges
10
Q
classical cadherins have
A
closely related sequences in their intracellular and extracellular domains
11
Q
nonclassical cadherins are
A
are more distantly related in sequence
12
Q
intracellular domains of cadherin are
A
more diverse because IC domain interact w many unique things
13
Q
the _ of cadherins interact in the _
A
amino termini of cadherins interact in the extracellular space between adjacent cells
14
Q
how do cadherins bind
A
- end domains of cadherin contain a knob and pocket
- knob of one cadherin insert into pocket of another
- distance between cells determined by structure of cadherins
15
Q
cadherin interactions are regulated by
A
extracellular Ca levels
16
Q
how are cadherin interactions regulated
A
binding of Ca to hinge regions prevents EC domains from flexing, resulting in a slightly curved rod
* without Ca, hinges are flexible and the cadherin domains become floppy
* w/o Ca, reduced affinity between cadherins
16
Q
how are cadherin interactions regulated
A
binding of Ca to hinge regions prevents EC domains from flexing, resulting in a slightly curved rod
* without Ca, hinges are flexible and the cadherin domains become floppy
* w/o Ca, reduced affinity between cadherins
17
Q
cadherins bind to each other with
A
low affinity ( weak bonds)
18
Q
how do cadherins form a strong junction
A
clusters of cadherins on one cell bind to clusters of cadherins on another
* accumulation of many weak bonds form velcro effect
19
Q
cell sorting is mediated by
A
cadherins
20
Q
cell sorting is mediated by
A
cadherins
21
Q
cell sorting by cadherins explained
A
cell sorting recognize based on type and level of cadherin expression
* same cadherins stay together, more expression make inner layer called primary ball which has tighter interactions
22
Q
_ is important for developmet
A
differential expression of cadherins
23
Q
switching off of _ can allow cells to dissociate and form migrating cells
A
E-caderin
24
mutations that disrupt _ are found in cancer cells
production of E cadherins
25
in adherens unctions,
the intracellular domains of cadherins are indirectly linked to actin filaments
| proteins in between them that link the two
26
adhesion belt
networks of actin filaments of adjacent cells connected via adherens juctions, located just beneath the apical surface of an epithelium
27
contraction of adhesion belt
provides the force required to fold epithelial sheets during development
* invagination pinches off to form tubes, vesicles and other structures
28
desmosomes are
clusters of non classical cadherins forming spot like welds that link intermediate filaments networks of adjacent cells
| snaps NOT velcro
29
desmosomes are
clusters of non classical cadherins forming spot like welds that link intermediate filaments networks of adjacent cells
| snaps NOT velcro
30
plakoglobin and plakophilin are used
cadherins linking to IFs
31
tight junctions enable _ by
unidirectional transport, by preventing molecules from passing between cells and the movement of transporters between apical and basaolateral domains
32
tight junctions form seals between
adjacent epithelial cells
33
in freeze-fracture, tight junctions
appear as branching network of sealing strands encircling the apical membrane
34
structure of tight junctions
* sealing strans of occludin and claudin proteins extracellular domains adhere and bring the lasma membranes into close proximity
* makes a tight junction
34
structure of tight junctions
* sealing strans of occludin and claudin proteins extracellular domains adhere and bring the lasma membranes into close proximity
* makes a tight junction
35
tight junctions are composed of three types of transmembrane proteins
claudin, occludin, tricellulin
36
claudin
* most abundant isoform
* essential for formation and function of tight junctions
* losds is fatal
37
occludin is important
* important for limiting the permeability of tight junctions
38
tricellulin is required
to seal membranes and prevent paracellular leakage at the junction points between three cells
39
ZO proteins
* bind to the cytoplasmic domains of adhesion proteins
* function as scaffold proteins that provide a structural support on which the tight junction is built
40
gap junctions form
direct passageways between cells
41
gap junctions structure
* 6 transmembrane **connexin proteins ** assemble into a hemichannel connexons
* connexons of two adjacent cells align to form an aqueous channel connecting the cytosols of the cells
42
size of gap junctions vary
with the number of connexons in the cluster pairs that form gap junctions
43
connexons can be
homomeric or hetromeric
44
regulation of gap junctions
* switch between open and closed states in response to many things
45
turnover of gap junctions
* new connexons are added to the periphery of a gap junction
* old connexons are removed from the center
* very rapid turnover rate
* before they are connexon, they are unpairs hemichannels
46
gap junction role in muscle
electrically couple cardiac and smooth muscle cells so there is no delay and there is synchrony (ex heart beat)
47
selectins are
cell surface, carbohydrate binding proteins with a conserved lectin domain
48
selectins are
cell surface, carbohydrate binding proteins with a conserved lectin domain
49
L selectin are found in
white blood cells
50
emigration of white blood cells at sites of inflmmation
1. cytokines are release
2. epithelial cells express E selectin
2. rolling: selectin binds to carbohy on leukocytes weakly so that the leukocyte can roll along the vessel wall
3. adhesion integrinds bind to ICAMs and the attachement of leuk to epith cell is stronger
4. leuk can stop rolling and squeeze through in between epith cells to escape
51
Tissues are composed of
cells and the ECM
52
Components of ECM
1. Fibers (insoluable): Collogen, Elastic
2. Ground Substance (soluable): Glycosaminogllycans, Proteoglycans, Multi domain glycoproteins
53
Glycosaminoglycans are
unrbanched polysaccharide chains composed ofo a repeating disaccharide units
* very high negative charge, causing sugars to be repealed by each other and spread out and take up a lot of volume
54
GAGs negative charges...
attract positive ions and water, so they form hydrated gels that resist compression
55
hyaluronan
a unique GAG that is v large and has no sulfated sugars and is not linked to a protein core
56
proteoglycans are composed of
GAG chains covalently linked to a core protein
* core protein and GAG chains point out like a bristles of a straw cleaner
57
proteoglycan synthesis
* core protein is synthesized by membrane bound ribosomes
* in the golgi, linkage tetrasaccharide is attached to a serine side chain on the core protein
* GAG residues are added to the tetrasaccharide one sugar at a time
58
decorin
proteoglycan that has one GAG, binds to collagen fibrils and regulates their assembly
59
aggrecan
proteoglycans that has a lot of GAGs, main proteoglycan in cartilage
60
proteoglycans can regulate
the activities of secreted proteins by binding to the secreted signal molecules and regulating their diffusion through the matrix
61
cell surface proteoglycans
integral components of the plasma membrain, core protein is inserted across the plasma membrane or attached via a GPI anchor
62
_ is the most abundant protein in animals
collegen
63
collegen molecules structure
* made up of three alpha chains wound around one another in a ropelike superhelix
* alpha chains are made up of a series of triplets Gly-x-x
* glycine is small so the alpha chains are closely packed
64
type one collagen are found in the
skin and bones
65
collagen fibrils are formed by
collagen molecules aligned head to tail in overlapping rows
66
collagen fibers are
bundles of collagen fibrils
67
fibral associated collagens
* the helical structure of alpha chains are interupted by non helical domains
* more flixible that fribrillar collagens
* kinks of the molecules allow it to form attaches to the ECM
68
network forming collages
* do not form fibrils
* form networks instead
69
network forming collages
* do not form fibrils
* form networks instead
70
what types of collegens dont form fibrils
* fibril associated collagens (type 9)
* network forming collagens (type 4)
71
elastic fibers structure
* elastin core
* periphery made of microfibrils that provide the scaffold for elastin
72
elastin structure
* alternating hydrophilic and alpha helixes
73
mutations in _ results in _ syndrome which is a relatively common tissue disease
fibrillin, Marfan's syndrome
| causes lens displacement
74
mutations in _ results in _ syndrome which is a relatively common tissue disease
fibrillin, Marfan's syndrome
| causes lens displacement
75
elastic fibers form _ which allow
coils which allow the fibers to stretch under stress
76
elastin molecules are held together by
linker proteins
77
multi domain glycoproteins
* have multiple binding sites
* function to organize matrix, attach cells to the ECM or guide cell movements in developing tissues
78
fibronectin structure
* composed of two very large similar subunits held together by disulfide bonds at c termini
* each subunit is folded into multople functionally distinct domains seperated by flexible hinge regions
| type of multidomain glycoprotein
79
fibronectin structure
* composed of two very large similar subunits held together by disulfide bonds at c termini
* each subunit is folded into multople functionally distinct domains seperated by flexible hinge regions
| type of multidomain glycoprotein
80
RGD
tripeptide repeat that is located in the type 3 fibronectin repeats, binds to integrins on the surface of the cell
81
binds to integrins on the surface of the cell
tripeptide RDG
82
insoluable fibernecton fibrils are formed in th eECM when
dimers are cross linked by additional disulfide bonds at the surface of cells (ex. with integrins)
83
when fibronectin molecules linked to actin cytoskeleton via integrins are stretched...
hidden binding sites ar exposed which allows them to bind to other fibronectin molecules
84
fibrils are only assembles _ because _
assembeled when needed because stretch is required for assembly
85
the basal lamina is
tough flexible sheet of specialized ECM
86
the basal lamina underlies
epithelial tissues, directly surround muscle, adipocytes and schwann cells, form part of the filteration barrier in kidney cells
87
components of the basal lamina
| listed
* laminin
* type IV collagen
* nidogen
* perlecan
88
laminin is
the primary organizer of the basal lamina
89
laminin structure
* composed of three chains (alpha, beta and gamma) arranged as an assymetric cross held together by disulfide bonds
* display binding sites for cell surface receptors and other components of the basal lamina
90
laminin heterotrimers require _ to assemble into _
require cell interaction to organize into a orderly sheet
91
type 4 collagen molecules
Network-forming collagen essential for the formation of the basal lamina, it forms a flexible, felt-like network that gives the basal lamina its tensile strength
92
Perlecan
Proteoglycan which links the laminin and type IV networks of the basal lamina
93
Nidogen
Along with the proteoglycan perlecan, this protein functions to link the laminin and type IV collagen networks of the basal lamina
94
assembly of basal lamina
* laminin network forms the initial sheet by binding to the cell surface recetors integrin and dystroglycan
* linkers perlecan and nidogen attach to the collagen IV network to the laminin network
95
agrin
specialized junctional basal lamina contains agrin and directs the regenerating nerve and new AceCh receptors
96
degradation of matrix is controlled by
* local activation
* secretion of inhibitors to protect other cells
* surface receptor controlled
makes sure onlt the ECM needed is destroyed
97
matrix metalloproteases
degrade matrix components, require Ca or Zn
98
serine proteases
degrade matrix components, highly reactive serine in their active sites
99
hemidesmosomes link
epithelial cells to the basal lamina
100
intracellular attachment to keratins is mediated by the adaptor proteins
plectin and BP230
101
Glanzmann's disease
Disease caused by a deficiency in the b3 subunit of integrin, resulting in defective clotting and excessive bleeding
102
Glanzmann's disease
Disease caused by a deficiency in the b3 subunit of integrin, resulting in defective clotting and excessive bleeding
103
Leukocyte adhesion deficiency
Disease caused by a deficiency in the b2 subunit of integrin, resulting in repeated bacterial infections
104
integrin outside in activation
binding of external ligand to EC domain causes EC domain to unfold and straighten, IC domain move apart, talin binding site is exposed, IC binds to cytoskeleton
105
integrin inside out activation
talin binds, EC domain unfolds and binds ECM component
106
talin competes
with alpha subunit to bind on beta chain
107
inside out activation depends on
intracellular regulator signals that stimulate the ability of talin and other proteins to interact with the beta chain of integrin
| thrombin present -> Rap1 active -> talin interact w beta ch -> bind CS
108
Junction which brings the plasma membranes of adjacent cells into close proximity, preventing the paracellular passage of most soluble molecules.
tight junction
109
Junction which allows for the passage of small molecules between the cytosols of adjacent cells
gap junction
110
A molecule consisting of a core protein with one or more attached GAG.
proteoglycan
111
Fibrous protein, rich in glycine and proline that confers tensile strength to the extracellular matrix.
collagen
112
Fibrous protein, rich in glycine and proline that confers tensile strength to the extracellular matrix.
anchorage dependent
113
_ are the most negatively charged molecules in animals.
Glycosaminoglycans
114
Members of the cadherin family function as the adhesion proteins in
both adherens junctions and desmosomes.
115
Both _ have binding domains for the linkers perlecan and nidogen.
laminin and type IV collagen
116
TRUE or FALSE: Unlike conventional ion channels, gap junctions are always in an open conformation.
False (Like conventional ion channels, gap junctions are not always open)
117
_ is a unique GAG containing non-sulfated sugar residues.
Hyaluronan
118
Type _ collagen is essential for the formation of the basal lamina.
IV
119
Mixtures of cells expressing two different cadherins will sort _ while mixtures of cells expressing different levels of the same cadherin will sort _
into two aggregates, into two layers of the same aggregate.
120
P-selectin is displayed on the surface of
blood platelets and endothelial cells activated by inflammatory response
121
Matrix molecules which display multiple binding sites for components of the ECM and cell surface receptors.
multi-domain glycoproteins
122
Cadherins promote cell-cell interactions by
binding to cadherin molecules of the same or closely related subtype on adjacent cells.
123
Proteoglycan can form
noncovalent attachments, via a linker protein, to hyaluronic acid to form large proteoglycan aggregates
124
4 phases of cell cycle
M phase, G1 phase, S phase, G2 phase
125
prophase
* condensation of sister chromatids
* mitotic spindle assembles
* condensin complex forms
* centrosome maturation
126
prometaphase
* nuclear envelope diassembles
* chromatids attache to spindle
* nuclear lamins phosphorylated
* nuclear pore complexes are phosphorylated
* formation of kineticore fiber
127
metaphase
* chromosomes align at metaphase plate
* microtubles flux
*
128
anaphase
* Poleward movement of chromosomes
* M-Cdks active
* Securin is ubiquitylated by APC/C
129
telophase
* mitotic spindle disassembles
* nuclear envelope reforms
* Gene transcription resumes
130
cytokinesis
* cytoplasm division
* Midbody forms
* RhoA activates formins
131
cytokinesis
* cytoplasm division
* Midbody forms
* RhoA activates formins
132
G1/S checkpoint aka start checkpoint
* make sure favorable conditions, cell procede S
* or pause in G1 or go to G0
133
G2/M checkpoint
* to eneter mitosis
* cellls not pass unless DNA repolication is complete and all DNA damage repair
134
metaphase to anaphase transition
* cells not pass unless chromosomes are properly attached to mitotic spindle
135
Cdks are regulated by
cyclins. Cdks must be bound to cyclin to be able to phosphorylate proteins
136
_ cycle active during G1
G1/S cyclin
137
cylclin active during S, G2, part of M
S cyclin
138
how does cyclin activate Cdk
* binding partially activates by pulling T loop away from active site
* full activation requires CAK to phosphorylate an amino acid near Cdk active site
139
Wee1
inhibits Cycl-Cdk
140
Cdc25 phosphatase
activates cyclin-Cdk
141
APC/C
* destroy S amd M cyclin to be able to go through metaphase ot anaphase checkpoint
* allows completion of M phase and cytokinesis
* targets securin that holds together mitotic spindle
142
APC/C is activated by
* mid mitosis by Cdc20
* late mitosis by Cdh1
143
SCF is _ during the cell cycle
constant but state of target changes
144
SCF
ub Cdk inhibitors in late G1
* triggers DNA replication
* activated by association with F box proteins
* only recognizes phosphorylated proteins
145
Pre-RC
formed in late mitosis to early G1, called the licensing of replication
* disassembled with DNA synthesis starts in S phase
* Pre-RC cannot reassemble until the next G1 phase
* makes sure DNA Is only replicated once
146
assembly of Pre-RC
ORC bind to OR and Cdc6 and Cdt1 help to bring DNA helicases to site
147
assemble of PreRC inhibited by _ and stimulated by _
Cdk, APC/C
148
Pre-Rc disassembled during
S phase
* S Cdk phosphorylates and ibhibits the ORC and Cdc6 proteins
149
PreRCs assemble in
early G1
* APC/C triggers destruction of Cdt1 inhibitor germinin
* inactivation of Cdks
150
cohesion complex made of
Smc3 and Smc1 and glues together sister chromatids
151
early mitosis is triggered by
abrupt increase in M-Cdk activity at G2/M checkpoint
152
anaphase triggered by
activation of APC/C (inhibit S and M Cdks)
* degregation of securin and cyclins
153
activation of M-Cdk
* M-Cdk accumulates during G2 and M phase due to increased synthesis of M-cylin
* M Cdk initially inactive due to phosphorylation of inhibitor sites by Wee1
* M-Cdk activated by Cdc25
* POsitive feedback increase M Cdk activation
154
Centrosome duplication begins in
S phase
155
resolution and condenstation of chromosomes in
Prophase
156
condensin complex triggered by
M-Cdk
157
maturation of chromosomes in
prophase
| up nucleation of MT
158
dynein motors role in centrosome speration
attach cell cortex to astral microtubles and pull centrosomes to opposite ends of chromosomes
159
kinesin 5 motors centrosome speration
attach to interpolar microtubles and push centrosomes part
160
minus ends kinesin 14 role in centrosome speration
attach to interpolar microtubles and pull centrosomes closer together
161
nuclear lamins are phosphorylated in _ by _
in prometaphase by M-Cdk
162
attachment of chromatids to kinetochore microtubles happens in
prometaphase
163
separase cleaves
the Scc1 subunit of the cohesin complex
164
MT attachement to kineticore mediated by
Ndc80
165
MT attache to kineticore in
mid prometaphase, complete attachment complete in metaphase
166
MT flux excert
force towards the poles
167
as kinesine walk towards the plus ends of the MT,
the attached chromosome is pulled away from the pole
168
sister chromatids freeing
before anaphase, securin binds to and inhibits a protease called seperase
* APC/C ub securin, activating seperase
* seperate cleaves Scc1 subunit of cohesin
* this frees the sister chromatids
169
contractile ring assembles during
anaphase
