process extension/growth cone Flashcards

(55 cards)

1
Q

what are the three steps of process navigation

A

detection of ligand and receptor
cytoplasmic signaling
motile response

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2
Q

what is involved in detection of ligand by the receptor

A

growth factors, chemoattractant and ECM. PTK receptors, cell adhesion molecules and neurotransmitters

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3
Q

what is involved in cytoplasmic signaling

A

calcium influx, protein kinase phosphatase, Rho/Rac/CDC42, IP3 and PIP2

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4
Q

what is involved in motile responses

A

actin-myosin and binding proteins, microtubules and binding proteins, GAP43 (growth associated protein), membrane flow

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5
Q

how is Rho active?

A

when bound to GTP

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6
Q

what causes faster turnover of Rho activity?

A

Rho GAP.

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7
Q

what causes slower Rho activity

A

Rho GDI

GDP-dissociation inhibitor

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8
Q

what causes increased Rho activity

A

Rho GEF. GTP exchange factor

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9
Q

what factors activate neurite extension, what evidence

A

Rac, CDC42, RhoG

activated versions enhance neurite outgrowth

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10
Q

what factors inhibit neurite extension or cause neurite retraction, evidence

A

RhoA

clostridium, blocks RhoA, blocks growth cone collapse

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11
Q

what does Rac do and in what cellular system

A

actin polymerization in the lamelipodia

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12
Q

what does Rho do and in whatcellular system

A

actin bundling in stress fibers

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13
Q

what does CDC42 do and in what cellular system

A

actin polymerization in filapodia

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14
Q

CDC42 mechanism

A

binds PIP2 and N-WASP and uses GTP to activate Arp2/3 to cause branching of actin filaments (70 degrees)

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15
Q

Rho family mechanism

A

rho family activity causes confirmational change in ERM (ezrin, radixin, moesin) proteins which causes binding to icams and F-actin

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16
Q

regulation of cofilin by Rho family

A

activation of Rho activates LIMK which stabilizes actin polymerization by phosphorylating cofilin.

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17
Q

regulation of cofilin by Rac

A

same as Rho family

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18
Q

how does slingshot regulate cofilin

A

it dephosphorylates cofilin which then causes F-actin severing and depolarization

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19
Q

ENA/Vasp proteins in process extension

A

binds Lpd membrane proteins, linking them to F-actin. this stabilizes the association between the membrane and F-actin

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20
Q

how do Rho family proteins regulate actin polymerizatoin

A

through activation of PAK, WASP, ERM and cofilin

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21
Q

how do ENA/VASP proteins regulate actin dynamics

A

cell surface receptor, actin/profilin binding, filamentous actin binding, by blocking actin capping proteins

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22
Q

how does membrane flow work in process extensino

A

1) membrane is endocytosed from areas not actively extending
2) membrane is generated de novo and transported through the golgi network

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23
Q

secretory mutants cause defects in what?

A

dendrites, not axons.

laser ablation of golgi outposts cause dendrite outgrowth defects.

24
Q

what regulates kinesin-dependent axonal growth

A

UNC-69/73. they link kinesin motors to vesicles

25
what is an intact secretory pathway required for?
dendritogenesis
26
does ER-to-golgi transport affect growth of axons
no
27
dendritic branches require what
golgi outposts
28
how are microtubules oriented in axons
in a uniform manner plus-end-distal.
29
what are par genes for
asymmetric orientations. they distinguish anterior and posterior poles of the embryo
30
par1
S/T kinase MARK in mammals
31
par 2
ring finger protein (ubiquitin pathway
32
par3
PDZ domain protein (scaffold)
33
par 4
S/T kinase (LKB1 in mammals)
34
par5
member of the 14-3-3 pathway
35
par6
PDZ scaffold
36
par 3/6 localization
apical pole
37
par 1/2
localized to lateral basal
38
par 4/5
equally distributed
39
are distinct domains actively maintained? how?
yes. by phosphorylation
40
apical domain sequestration
aPKC phosphorylates par-1 leading to par-5 binding, preventing association with the membrane
41
lateral domain
par-1 phosphorylates par-3 releasing it from the membrane
42
what proteins are required for establishing the apical/basal regions
par proteins, aPKC/CDC42
43
what is the first polarizing event in neurons
axonogenesis
44
what happens when you sever an axon
new axon formatino
45
what factor causes supranumery axons
cytochalazin D
46
where does mPar6 localize
tip of nascent axon
47
what factor is required for axon initiation
aPKC
48
what can we inhibit to block polarization
PI3K
49
how is LKB1 regulated
binding STRAD and MO25 recruits it to the cytoplasm, stabilizes it and activates it kinase activity
50
what are the downstream substrates of LKB1
MARK (Par1) and SAD kinases
51
what does inactivation of LKB1 causes what
peutz-Jaghers cancer syndrome
52
what does STRAD expression do
stabilizes LKB1 in one process prior to axon specification
53
what happens when LKB1 inactivated
loss of axon initiation
54
LKB1 + STRAD = ?
more axons
55
how is axon/dendrite polarity initiated
neuronal migration