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BMS2002 > L21 > Flashcards

L21 Flashcards

1
Q

what does asymmetric cell division in stem cells

A

balances proliferation and self-renewal with cell-cycle exit and differentiation

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2
Q

give examples of cells that can undergo ACD

A

stem cells

germ cells

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3
Q

what does too much cell renewing capacity lead to

A

hyperproliferation cancer

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4
Q

what does insufficient production of proliferative cells lead to

A

tissue degeneration and aging

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5
Q

what does ACD in germ cells produce

A

Rejuvenated
Cell linage
- differentiates into sex cells

Less fit cell
(senescence
factors)
- contain detrimental things

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6
Q

what are the types of ACD

A

cell intrinsic

cell extrinsic

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7
Q

what does intrinsic mean

A

ACD starts prior to the division process

cell fate factors are inherited by differentiating cell

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8
Q

what does extrinsic ACD mean

A

requires extracellular signaling for differentiating cell

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9
Q

what organisms was studied for ACD

A

drosophila

C. elegans

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10
Q

what are the steps of ACD

A
  1. Establishment of polarity axis in interphase
  2. Use polarity axis for orientation of mitotic spindle and segregation of cell fate determinants in mitosis
  3. Coordination between spindle orientation and cell fate determinant positioning to ensure that only one of the daughter cells will inherit the cell fate determinant
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11
Q

what does cell polarity depend on

A

asymmetric localization of polarity regulators

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12
Q

what are the steps involved in Polarisation of the C. elegans zygote by the PAR proteins

A

male pronuclous bring in the centrosomes

centrosomes start a signal (Aurora A
kinase) from the posterior complex that induce cell polarisation as PAR proteins are accumulated asymmetrically

Acto-myosin network is interlaced by myosin motor concentration (foci)

foci assemble and disassemble, creating tension

this leads to Acto-myosin flow polarisation into anterior complex
(RHO1 and CDC42 dependent process)

this leads to PAR advection and underlying cytoplasm movement to the anterior part of the cell

centrosomes also regulate the positioning of the posterior parts by allowing them to accumulate at the membrane

this is done by inhibition (phosphorylation) of PKC-3 in the posterior part

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13
Q

how is ant-PAR proteins and post-PAR proteins distribution maintained with no boundary

A

they inhibit each other

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14
Q

give examples of post-PARs

A

PAR-1

PAR-2

LGL-1

CHIN-1

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15
Q

give examples of ant-PARs

A

PAR-3

PAR-6

PKC-3

CDC-42

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16
Q

what does PAR-1 inhibit

A

PAR-3

17
Q

what does CHIN-1 inhibit

A

CDC-42

18
Q

what does PKC-3 inhibit

A

all post-PARs

19
Q

describe Stem cell (neuroblast) asymmetric division in fruit fly

A

extrinsic ACD

Polarity inherited from the neuroectoderm

PON, marinda, Numb, BRAT and Prospero all localise at the basal part of the cell

PAR3,PAR6, aPKC and inscuteable all localise at the apical part of the cell

apical part of the cell divides into a self-renewal cell.

basal part divides into GmC which differentiates into neurons

20
Q

what happens when Posterior PARs are depleted

A

mitotic spindles move slowly to the cell axis

21
Q

describe the mitotic spindle positioning machinery

A

dynein walks on the tubules to the minus end carrying LIN-5 inked to GPR-1/2 which interacts with G alpha on the membrane pulling the tubule to the membrane.

PARs regulate the machinery e.g. LGN in the posterior part

phosphorylation of NUMA by Aurora A production, CDK1 and aPKC inhibition reduces the function of the complex in the anterior

therefore, pulling forces start in anaphase

22
Q

what complex is balanced in Mitotic spindle orientation in asymmetric stem cell division (neuroblast) with the Force generating
complex (dynein involving)

A

spindle capturing complex

involves kinesin motors which move to the positive end of the tubules

23
Q

describe centrosome stereotypical positioning

A

Another way to determine spindle orientation

Centrosome is recruited to the
apical crescent

Daughter centrosome remains apical
and presents more microtubule polymerization activity

Mother centrosome sheds peri central material (PCM) (decreased activity) Favoring the orientation of the forming spindle

Mother centrosome will be inherited
by the cell undergoing differentiation

24
Q

How do cells transduce cortical polarity to cell fate determinant in asymmetric segregation of C. elegans zygote

A

through the activity of MEX-5 and P granules

25
Q

what does MEX-5 do

A

MEX-5 at the anterior promotes the degradation of germ plasm proteins (ensures somatic specification)

PAR-1 phosphorylates MEX-5 in the posterior leading to fast movement of MEX-5 in the cytoplasm

LET-92 dephosphorylates MEX-5 in the anterior slowing its movement

26
Q

what are P granules

A

P granules are condensates of proteins and RNA that are inherited by the germ linage

27
Q

what do P granules do

A

they dissolute in the interior

they condense in the posterior leading to a flux because condensed P granules deplete from the components around them

28
Q

what does aPKC do in Stem cell (neuroblast) asymmetric division in fruit fly

A

Targets Numb and Miranda

promoting differentiation and inhibit cell renewal in different ways

29
Q

how does Numb different in the basal and apical

A

Numb is phosphorylated in the apical

phosphorylated Numb moves to the basal to promote differentiation

30
Q

what does aPKC to miranda

A

it phosphorylates it in the apical

31
Q

how does polarity help position the cell cut

A

Polarity -> orients the mitotic spindle
Mitotic spindle -> helps position the cut

32
Q

how is the final cut (cytokinesis) positioned

A

Astral MT inhibit cortical contractility (AuroraA) by preventing myosin accumulation at the poles

The central-spindle and cell cycle regulators help activate and place the cytokinetic furrow

involves cell cycle components

33
Q

what is the role of AurA in drosophila neuroblasts

A

AurA promotes aPAR
complex assembly

34
Q

what is the role of AurA in C. elegans zygotes

A

AurA -> Plk1 inhibits aPAR premature cortical localisation

BMS2002 (21 decks)

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