L21 Flashcards
what does asymmetric cell division in stem cells
balances proliferation and self-renewal with cell-cycle exit and differentiation
give examples of cells that can undergo ACD
stem cells
germ cells
what does too much cell renewing capacity lead to
hyperproliferation cancer
what does insufficient production of proliferative cells lead to
tissue degeneration and aging
what does ACD in germ cells produce
Rejuvenated
Cell linage
- differentiates into sex cells
Less fit cell
(senescence
factors)
- contain detrimental things
what are the types of ACD
cell intrinsic
cell extrinsic
what does intrinsic mean
ACD starts prior to the division process
cell fate factors are inherited by differentiating cell
what does extrinsic ACD mean
requires extracellular signaling for differentiating cell
what organisms was studied for ACD
drosophila
C. elegans
what are the steps of ACD
- Establishment of polarity axis in interphase
- Use polarity axis for orientation of mitotic spindle and segregation of cell fate determinants in mitosis
- Coordination between spindle orientation and cell fate determinant positioning to ensure that only one of the daughter cells will inherit the cell fate determinant
what does cell polarity depend on
asymmetric localization of polarity regulators
what are the steps involved in Polarisation of the C. elegans zygote by the PAR proteins
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
how is ant-PAR proteins and post-PAR proteins distribution maintained with no boundary
they inhibit each other
give examples of post-PARs
PAR-1
PAR-2
LGL-1
CHIN-1
give examples of ant-PARs
PAR-3
PAR-6
PKC-3
CDC-42
what does PAR-1 inhibit
PAR-3
what does CHIN-1 inhibit
CDC-42
what does PKC-3 inhibit
all post-PARs
describe Stem cell (neuroblast) asymmetric division in fruit fly
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
what happens when Posterior PARs are depleted
mitotic spindles move slowly to the cell axis
describe the mitotic spindle positioning machinery
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
what complex is balanced in Mitotic spindle orientation in asymmetric stem cell division (neuroblast) with the Force generating
complex (dynein involving)
spindle capturing complex
involves kinesin motors which move to the positive end of the tubules
describe centrosome stereotypical positioning
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
How do cells transduce cortical polarity to cell fate determinant in asymmetric segregation of C. elegans zygote
through the activity of MEX-5 and P granules
what does MEX-5 do
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
what are P granules
P granules are condensates of proteins and RNA that are inherited by the germ linage
what do P granules do
they dissolute in the interior
they condense in the posterior leading to a flux because condensed P granules deplete from the components around them
what does aPKC do in Stem cell (neuroblast) asymmetric division in fruit fly
Targets Numb and Miranda
promoting differentiation and inhibit cell renewal in different ways
how does Numb different in the basal and apical
Numb is phosphorylated in the apical
phosphorylated Numb moves to the basal to promote differentiation
what does aPKC to miranda
it phosphorylates it in the apical
how does polarity help position the cell cut
Polarity -> orients the mitotic spindle
Mitotic spindle -> helps position the cut
how is the final cut (cytokinesis) positioned
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
what is the role of AurA in drosophila neuroblasts
AurA promotes aPAR
complex assembly
what is the role of AurA in C. elegans zygotes
AurA -> Plk1 inhibits aPAR premature cortical localisation
