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developmental final > process extension/growth cone > Flashcards

process extension/growth cone Flashcards

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
Q

what is an intact secretory pathway required for?

A

dendritogenesis

26
Q

does ER-to-golgi transport affect growth of axons

A

no

27
Q

dendritic branches require what

A

golgi outposts

28
Q

how are microtubules oriented in axons

A

in a uniform manner plus-end-distal.

29
Q

what are par genes for

A

asymmetric orientations. they distinguish anterior and posterior poles of the embryo

30
Q

par1

A

S/T kinase MARK in mammals

31
Q

par 2

A

ring finger protein (ubiquitin pathway

32
Q

par3

A

PDZ domain protein (scaffold)

33
Q

par 4

A

S/T kinase (LKB1 in mammals)

34
Q

par5

A

member of the 14-3-3 pathway

35
Q

par6

A

PDZ scaffold

36
Q

par 3/6 localization

A

apical pole

37
Q

par 1/2

A

localized to lateral basal

38
Q

par 4/5

A

equally distributed

39
Q

are distinct domains actively maintained? how?

A

yes. by phosphorylation

40
Q

apical domain sequestration

A

aPKC phosphorylates par-1 leading to par-5 binding, preventing association with the membrane

41
Q

lateral domain

A

par-1 phosphorylates par-3 releasing it from the membrane

42
Q

what proteins are required for establishing the apical/basal regions

A

par proteins, aPKC/CDC42

43
Q

what is the first polarizing event in neurons

A

axonogenesis

44
Q

what happens when you sever an axon

A

new axon formatino

45
Q

what factor causes supranumery axons

A

cytochalazin D

46
Q

where does mPar6 localize

A

tip of nascent axon

47
Q

what factor is required for axon initiation

A

aPKC

48
Q

what can we inhibit to block polarization

A

PI3K

49
Q

how is LKB1 regulated

A

binding STRAD and MO25 recruits it to the cytoplasm, stabilizes it and activates it kinase activity

50
Q

what are the downstream substrates of LKB1

A

MARK (Par1) and SAD kinases

51
Q

what does inactivation of LKB1 causes what

A

peutz-Jaghers cancer syndrome

52
Q

what does STRAD expression do

A

stabilizes LKB1 in one process prior to axon specification

53
Q

what happens when LKB1 inactivated

A

loss of axon initiation

54
Q

LKB1 + STRAD = ?

A

more axons

55
Q

how is axon/dendrite polarity initiated

A

neuronal migration

developmental final (9 decks)

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