Cytoskeleton Flashcards
1
Q
What makes up protofilaments?
How many protofilaments in a MT?
A
Alpha and beta tubulins. Alt order
1 MT = 13 protofilaments
Alpha @ - end
Beta @ + end
2
Q
Which filaments are DYNAMIC
A
MTs and microfilaments
3
Q
Are protofilaments/ MTs polar? Which end what side?
A
YES, theyare POLAR
- @ centrosome
+ near cell PERIPHERY
4
Q
MT motor P’s:
Which MP goes + → -?
A
Dynein
Mn = dynein ~ dine in (towards cell)
Or dying is a NEGATive thing
5
Q
MT what is CATASTROPHE?
A
When the GDP bound tubulin reaches the growing end
→ it falls apart
6
Q
What does alpha and beta tubulin need to elongate?
A
GTP
7
Q
Rate of polymerization or depolymerization of muscle cells depends on ___
A
[GTP]
8
Q
Dynamic instability
A
MicroTUBULES
9
Q
Treadmilling
A
Actin (microfilament)
10
Q
Which tubulin hydrolyzes GTP→ GDP?
A
BETA tubulin
11
Q
Function of MTs
Singlets?
Doublets?
Triplets?
A
Singlets fn = TX VESICLES
Doublets fn = CILIA, FLAGELLA (axoneme)
Triplets fn = make up CENTRIOLES
12
Q
How manyy triplets are in a centriole?
A
9
13
Q
MTs: singlets fn
A
TX VESICLES, organelles and chromosomes
14
Q
MTs: doublets fn
A
CILIA
FLAGELLA
AXONEME
15
Q
MTs: triplets fn
A
Make up CENTRIOLES (9)
Basal bodies
MTOCs
16
Q
How many centrioles in a centrosome?
A
2
17
Q
T/F there are 9 MT doublets in a centriole?
A
FALSE
Centriole = 9 TRIPLETS
18
Q
What are the - ends of the MT ANCHORED IN?
A
MTOC
19
Q
T/F motor P’s have ATPase activity
A
True
20
Q
Where will you find the gamma tubulin
A
In the MTOC in the PERICENTRIOLAR material
@ ORIGIN (- end) of MTs
21
Q
What is the funciton of MT associate P’s? (MAP)
A
STABILIZE existing MTs
22
Q
What happens when you hyperpolarize tau?
A
They will CLUMP → forming NFTs
NFTs DESTABILIZE MTs → alzheimers
23
Q
What is the origin of MTs?
A
MTOCs (@ - end) & GAMMA tubulin
24
Q
What is the advantage of using MT motor P’s?
A
FASTER to get to destination
EFFICIENT
More accurate in going to correct destination
25
How many ATPase heads do MT motor proteins have?
2
26
What is the cause of Alheimers?
HYPERPHOSPHORYLATED TAU → forms NFTs = depol MT and bad axon tx
ACCUM of BETA-AMYLOID/ SENILE PLAQUES (EXTRACELLULAR)
27
Where in the cell will you find BETA-AMYLOID / SENILE PLAQUES?
EXTRAcellular
28
Where in the cell would you find NFTs?
INTRAneuronal
29
What does hyperphosphorylation of tau cause?
FORMS NFTs (intraneuronal)
ACCUM of beta amyloid plaques (extra)
30
What gene is a RISK FACTOR for alzheimers?
apo E4 = RF... NOT cause
31
How does apo E2 gene fx alzheimers?
↓ RISK
32
What kind of alheimers contain the following genes? & what inheritance is this?
PRESINILIN 1 & 2
BETA-amyloid precursor (trisomy 21)
EARLY ONSET
AD
33
Apo E4 gene is associated with what kind of alzheimers?
LATE ONSET
34
Genes associated with Early and Late onset alheimers =?
EARLY = PRESINILIN 1 & 2, BETA-amyloid
LATE ONSET = apo E4 = MULTIFACTORIAL
35
MULTIFACTORIAL (Alzheimers)
LATE ONSET
36
LATE ONSET alheimers
MULTIFACTORIAL
Apo E4 = RF
Apo E2 = ↓ Risk
37
Early onset Alzheimers: what is fn of PRESINILIN 1, 2 or BETA-amyloid?
MUT in these genes alter fn of SECRETASE
Secretase cleaves the beta-amyloid
Mut = longer strands of beta-amyloid peptide = diz
38
What is the fn of SECRETASE? What happens if it is mut?
CLEAVE beta-amyloid peptide
Mut = LONGER b-amyloid peptide = EARLY ONSET ALZHEIMERS
39
Mitotic spindle: fn of dynein
Attached to KINETOCHORE MTs
Brings chromos CLOSER
40
Mitotic spindle: Kinesin
Attached to POLAR MTs
Push off each other to ↑ DISTANCE btw CENTROSOMES
41
Axoneme
CILIA
| FLAGELLA
42
What is the axonemes MTOC?
BASAL BODY
43
What is the AXONEME?
The cytosk structure in CILIA and FLAGELLA
9x2 +2
Axoneme's MTOC = basal body
44
9x2 +2 arrangement
Axoneme
45
Structure of BASAL BODY
Complete (13 protofil) MT grow 2 out of 3 MTs in the 9 triplets of basal body
BASAL BODY = 9x3
CILIM = 2 OUT OF 3 of MT
46
Structure /arrangement of Cilia
Basal body = 9x3 (~ centriole)
| Cilium = 9x2 + 2 (in center)
47
BENDING in cilia and flagella is due to ___?
1) Dynein &
| 2) LINKAGE PROTEINS
48
DIZ of Immotile cilia & sperm
Primary ciliary dyskinesia
49
Immotile cilia & sperm leads to what?
| What diz is this?
INFERTILITY (sperm)
RETENTION OF SECRETIONS = RECURRENT INFXNS
50
What symp will you observe in Kartagener syn?
SITUS INVERSUS = inverted organs
Bronchiectasis (thickened bronchi)
Chronic paranasal sinusitis
Infertiliy
51
Why is there SITUS INVERSUS in KARTAGENER syn?
↓ ciliary activity = Defective cell motility during embryogenesis
52
Polar MT : __________
| Kinetochore MT : _____________
Polar MT : KINESIN
Kinetochore MT: DYNEIN
Mn: KD has a SHORT & CLOSE sister
53
Which drugs bind tubulin & PREVENT GROWTH / polymerization
Colchicine (gout)
VINcristine & VinBLASTine (CA with ↑ mitotic index)
Mn: VIN diesel BLASTs away growth
54
What does vincristine and vinblastine prevent?
Bind tubulin → PREVENT GROWTH
Prevents FORMATION OF MITOTIC SPINDLE → blocks cell in M phase
55
What does Paclitaxel (Taxol) do?
Bind and STABILIZE MTs (inhib depol)
BLOCKS MITOSIS (can't break ↓ mitotic spindle)
Treat CA
56
What CA drug inhibits DEPOLymerization?
Paclitaxel (taxol)
Mn: TAXes STABILIZE the nation's spending
Mn: TAXes are the reason that the gov CAN'T BREAK DOWN (mitotic spindle)
57
What drug causes:
1) inability to FORM mitotic spindle
2) inability to BREAK DOWN mitotic spindle?
1) Vincristine, Vinblastine
| 2) Paclitaxel (Taxol)
58
Intermediate Filaments = polar or non-polar?
NON polar
59
What is the basic structure of IFs?
8 TETRAmers
60
T/F: IF need ATP or GTP 4 polymerization
FALSE!
No ATP or GTP needed
Needs PHOS 4 pol/depolymerization
61
2 FNs of IFs
1) TENSILE STRENGTH (b/c of HEMIDESMOSOMES)
| 2) RESISTANCE to STRETCH (b/c of DESMOSOMES)
62
HEMIdesmosomes attribute to which fn of IFs?
TENSILE strength
63
What are the Motor proteins of IFs?
NONE
IFs have no fn with MPs
64
What are exmaples of NUCLEAR IFs?
LAMINS a, b ,c
65
What are the components of VIMENTIN like IFs?
Vimentin → fibroblasts, endothelial cells
Desmin → muscle
Glial fibrillary acidic P → glial cells
Peripherin → neurons
66
Desmin
MUSCLE
VIMENTIN-like IFs
Mn: DESMond green = athlete and has lots of MUSCLE
67
What are the components of EPITHELIAL type IFs?
Type I and II keratins
type I = acidic
Mn: A is the 1st letter in alphabet
Type II = basic
68
Type I keratin characteristics
ACIDIC
| Epithelial type IFs
69
keratin IFs that break in epithelial cells = ?
BLISTERING
70
Epidermolysis Bullosa Simplex = which keratins?
Location?
5 and 14
BASEMENT MEM
Mn = Bullosa = Basal (& 5 letters)
Mn; whats 9+10 video.. =19. 5+14 = 19 and that video is BS (bullosa simplex)
71
Epidermolytic Hyperkeratosis = which keratins?
Location fx'd?
1 and 10
SUPRABASILAR
Mn: scale of 1 to 10 surveys are HYPERactively used in MPH programs
72
Epidermolytic PLANTOPALMAR Keratoderma = which keratins?
9
Mn: Dogs (K9) like sniffing human's HANDS AND FEET
73
Fn of LAMINS
1) Lines INNER surface of NUC ENV
2) Structural stability
3) PROTECTS DNA
4) ANCHOR site 4 chromos, TFs & pores
74
Progeria = mut in what?
LAMIN A
75
What is the fn os neurofilaments (type of IF)
CROSS-linking of NFs STRENGTHENS long AXONS
76
What shape does Actin form?
actin monomer forms DOUBLE HELIX
77
Actin FN (3)
1) cell MIGRATION
2) structure
3) CYTOKINESIS
78
Which type of filament is responsible for cytokinesis?
ACTIN (microfilament)
Also does cell migration and structure
79
What is needed for Actin to grow / polymerize?
ATP
80
T/F Actin needs GTP to GROW
FALSE ....Needs ATP
GTP used by MTs
81
Which filaments are polar
MTs & Microfilaments (ACTIN)
82
What is the difference btw the + & - end of actin?
+ end = FAST growing
| - end = SLOW growing
83
what is the purpose of CAPPING in actin?
What Protein or whatever actually caps Actin
1) CREATES BOUNDARIES ... otherwise growing Actin would keep growing uncontrollably into spaces it shouldn't
2) Actin-ATP cap
84
What controls the rate of elongation/ shortening in actin?
ATP
85
If there is a ↑ [ATP] & ATP-G-actin, which end will the actin elongate from?
BOTH ends
86
↓ [ATP] leads to what in actin elongation?
TREADMILLING
Length stays the same. SAME RATE elongate from 1 side and break down from the other side
87
TREADMILLING : ______
| DYNAMIC INSTABILITY : ____
Treadmilling = F-ACTIN
| Dynamic instability = MTs
88
What is the relationship btw G-actin and F-actin
G-Actin POLYMERIZES into F-Actin (actin Filaments)
```
G-actin = globular
F-actin = filamental
```
89
MITOTIC SPINDLE = what type of filament?
MTs
90
What is needed 4 F-actin ELONGATION?
ARP complex (ARP 2/3)
91
Where can ARP complex be found?
What does it do?
- LEADING edge of MIGRATING CELLS (Actin)
- NUCLEATES (elongates) filaments (actin).
- works more efficiently when BOUND to side of PREEXISTING actin
92
What does ARP 2/3 do?
Bind actin monomer & STIM BUILDING NEW ACTIN fil
93
What nucleates (stim) growth of STRAIGHT UNBRANCHED actin?
What does it form/ product?
FORMIN
PARALLEL BUNDLES
94
CROSS LINKING actin-binding P's
COFILIN
GELSOLIN
Mn: CG wears a choker with CROSS LINKING design
95
SEVERING actin-binding P's
FILAMIN
FIMBRIN
VILLIN
96
What does Thymosin do?
Bind g - prev f
BINDS g-actin →
PREVENTS f-actin assembly
97
What does profilin do?
Binds G-actin → PROMOTES actin assembly @ + end
▵s Actin-ADP → actin-ATP
COMPETES with THYMOSIN
98
Thymosin vs Profilin
Both bind to G-actin
Thymosin = PREVENT f-actin assembly
PROfilin = PROmotes assembly @ + end
99
Cofilin
DISASSEMBLES @ - end
Mn; disassembly is a - thing
100
Gelsolin
CAPS + end
= prev further growth?
Mn: use GEL when I don't wear a CAP
101
To prevent actin from further growth and crossing boundaries, _____ is an actin binding protein that will (do) _____ to solve this issue
- GELSOLIN
CAP + end
Mn: i use GEL on my hair when I don't wear a CAP
102
Which myosin has CONTRACTILE activity?
MYOSIN II (in musc)
103
______ (3) form parallel cables/ bundles of actin
while _____ (2) form WEBS/GELS of actin
Parallel cable = ALPHA-actinin, FIMBRIN and VILLIN
Web = SPECTRIN and FILAMEN
Mn: you can SPECTate dr. FIL on the WEB
104
ALPHA-actinin properties
STRESS fibers
CONTRACTILE
LOOSE packing
105
What kinds of cross-linking p will you find in FOCAL ADHESIONS?
ALPHA - actinin
| Loose, contractile, stress
106
Fimbrin
NON-contractile
MICROVILLI
Tight
107
ALPHA -actinin can be found where? (2)
In STRESS fibers
Mn = ALPHA personality ppl STRESS me out
Within FOCAL ADHESIONs
108
What kinds of cross linking would you find in MICROVILLI?
FIMBRIN
109
Dystrophin
ANCHOR 2 SARCOLEMMA
Anchors actin cytosk 2 SARCOLEMMA in sk musc
110
Vinculin and Talin
FOCAL ADHESIONS
Attach actin cytosk to mem in focal adhesions
111
Which cross linking PREVENTS myosin II from entering bundle?
FIMBRIN
Because tightly packed
112
Alpha actinin
Loose so ALLOWS MYOSIN II to enter bundle
CONTRACTILE
Mn = Alpha is Contractile (AC) and AC makes people LOOSE /comfy
113
STEREOCILIA: what is a characteristic?
What is found in it?
NON-MOTILE
Packed with F-actin
In hair cells and empididymis
114
What is the fn of FILAMIN and where is it found? (Not fimbrin)
makes 3D CROSSLINKS
Found under PM
115
What ACTIVATES NUCLEATING P's (like arp)? Be specific
Rho GTPases -- 3 kinds
Lamellipodia = rac
Filipodia = cdc42
Stress fibers = rho
116
Lamellipodia = ____
Filipodia = ____
Stress fibers = ____
What do these all do?
Lamellipodia = rac ; MN = RACk of LAMb
Filipodia = cdc42
Stress fibers = Rho ; Mn= stress = ruh rho
All = RHO GTPases that ACT nucleating p's
117
What do Rho GTPase activate?
What do these 2 things do?
ARP 2/3 complex & Cofilin
ARP stim growth @ leading edge
Cofilin DEPOLs actin @ TRAILING edge
118
In cell movement, what does a cell need to make to MOVE FORWARD?
Cell needs to make NEW LAMELLIPODIA & FOCAL ADHESIONS
REAR contracts and PROPELLED forward
119
What does cofilin do??
DEPOL actin / break down
Mn: COFing BREAKS DOWN mucus in throat
120
WASP mutation diz?
Inheritance pattern?
WISKOTT -ALDRICH syn
SEVERE X-linked diz
NO WASP → NO ARP2/3 ACTIVATION
121
If WASP is mut, what does that lead to?
Bad WASP → no ARP 2/3 activation!
= no growing actin, DISRUPTION of signal pathways
=NO MIGRATION
Wiscott aldrich syn
122
What are the names of 3 drugs that BLOCK ACTIN FN?
Cytochalasins
Phalloidin
Latrunculin
123
T/F/ In musc contraction, myosin walks towards + end
TRUE
124
In relaxed state, where is the tropomyosin?
COVERS myosin binding site
Has troponin on it which Ca++ binds to
125
What does DESMIN do in musc?
Helps ALLIGN SARCOMERES
126
in the sarcomere, the ____ is often CAPPED with _____ @ the + end
F-actin
| Cap Z
127
sarcomere:
What caps the + end
What caps the - end?
+ end cap = Cap Z
| - end cap = Tropomodulin
128
What is the Z disc composed of?
Cap Z + alpha-actinin
129
Events in muscle contraction
Nerve Signal triggers action →
Sarco retic RELEASES Ca++ →
Ca++ bind troponin C →
tropomyosin moves and EXPOSES myosin binding site →
Myosin head binds!
130
Why does RIGOR MORTIS occur?
Dead body no longer makes ATP
Myosin NEEDS ATP to RELEASE from ACTIN
Ca++ can't be returned to SR
131
What diz seen with mut in Actin @ Z DISK
Dilated Cardiomyopathy (30% hereditary)
Symp = CHF, weak, fatigue, PE
132
67 yo pt complains with weakness and has previously been diagnosed with CHF. He has a family history of cardiac issues.
What is cause and diz?
Cause = mut in GENES encoding SARCOMERE, CYTOSK & NUC LAMINA
Z DISK ACTIN MUT
Diz = Dilated Cardiomyopathy
133
What is the CAUSE of an ASYMPTOMATIC / Mild sym diz that presents with CP, syncope, fatigue, SOB & palpitations?
What is the inheritance?
Mut in CARIDAC ISOFORMS (MYOSIN II, tropomyosin and troponin)
```
#1 sudden killer in athelete
AD
```
familial hypertrophic cardiomyopathy
134
CARDIAC ISOFORMS mut
Familiar hypertrophic cardiomyopathy
Kills athletes
Asymp
135
Becker md genetic defect
INFRAME insertion/deletion
136
What does DYSTROPHIN link?
Actin with dystroglycan beta (part of the glycoprotein complex)
137
What are the components of the dystroglycan complex?
Alpha dystroglycan = binds to ECM via laminin & sarcoglycans
Beta = links actin to ecm.
138
What is the sarcolemma?
Pm of sarcomere
139
Without dystrophin, what happens?
Loss of DAP @ sarcolemma
140
Absence of physical link of DAP
Fragile sarcolemma
141
What is happening with satellite cells in MD?
It is still trying to repair but repair can not keep up with repeated dmg → CT & fat accumulation
142
Rigor mortis
Dead so can't make ATP
ATP needed for myosin release from actin
Ca2+ not returned to SR
143
Cause of dilated cardiomyopathy
MUTATION IN ACTIN where it binds to Z DISK
Mut in genes encoding components of sarcomete, cytoskeleton & nuclear lamina
144
What is most commonly mutated in dilated cardiomyopathy?
TITIN
145
MUT in familiar rhypertrophic cardiomyopathy
Cardiac isoforms = myosin II, tropomyosin and troponin
146
What does dystrophin connect?
Actin 2 beta-dystroglacan (glycoP complex)
147
FN of dystrophin other than connect
Transduce contractile forces from intracell sarcomere to ECM
148
Fn of glycoP complex
Link actin to LAMinin 2
149
A-dystroglycan connects to __
Laminin & sarcoglycan
150
Beta dystroglycan
Binds dystrophin 2 glycoP complex
151
Fn of dystroglycan complex
Structural STABILITY DURINIG CONTRACTION
152
What diagnostic blood test can be used to test 4 MDs?
Look 4 ↑ serum CREATINE KINASE
153
DMD
TOTAL LOSS of DYSTROPHIN
Most SEVERE
Xp21 mut
3-5 yo
Genetically lethal in males
XD
FRAMESHIFT
Calf pseudohypertrophy
154
Becker MD
PARTIAL FUNCTION OF DYSTROPHIN
Inframe
Onset = late childhood
VARIABILITY
155
Emery-Dreifuss MD
EMERIN (or lamin a/c) mut
X-linked
Early contractures: elbow, neck, ankles
Pacemaker by 30yo
156
Myotonic Dystrophy
```
MYOTONIN P KINASE
TRINUC RPT DISORDER (CTG)
ANTICIPATION
Ptosis
Haggard
Multisystemic
```
157
Facioscapulohumeral MD
Deletion of SUBTELOMETRIC TANDEM RPT
Winged scap
158
Limb girdle MD
Mut SARCOGLYCANS
Same symptoms as DMD and BMD
Die frmo RESP FAILURE
159
Congenital muscular dystrophy
Mut in LAMININ
Contractures SEIZURES, MR
160
NO DYSTROPHIN =
LOSS OF DAP @ SARCOLEMMA
161
WHAT CAUSES A LOSS OF DAP @ SARCOLEMMA?
NO DYSTROPHIN
162
ABSENCE OF PHYSICAL LINK OF DAP = ___?
FRAGILE SARCOLEMMA?
163
WHY DO WE HAVE MD?
NO DYSTROPHIN =
LOSS OF DAP @ SARCOLEMMA =
NO PHYSICAL LINK =
FRAGILE SARCOLEMMA =
= MD DURING RPTD CYCLES OF CONRACTION AND RELAXATION
