Ch. 18 Control of Cell #s and Size, M Phase, Mitosis, Cytokinesis Flashcards
how can body and organ size be determined
cell growth, division, death
what is the most common form of programmed cell death
apoptosis
why is apoptosis necessary
due to body/organ dynamism (constantly having to respond to environment)
what is dynamism controlled by
cell birth and death rates
what process is apoptosis crucial to
sculpting
compare apoptosis and necrosis
- apoptosis: molecular pathways which complete internal degradation leading to engulfment by phagocytic cells (“clean”)
- necrosis: spewing of cellular contents into environment (“messy”)
describe necrosis and when it would occur
physical or chemical damage to cell (esp to plasma membrane) causes all cellular contents to release
what triggers apoptosis
caspase molecules
draw out how apoptosis would would be triggered
main points: initiator procaspase dimerizes, activates, and cleaves into an active form (initiator caspase); this active form would activate executioner procaspases thru cleavage causing caspase cascade leading to apoptosis
describe the initiator procaspase structure
- adaptor binding region
- protease domain which has protease properties
- monomers
how can initiator procaspases be activated
when an apoptotic stimulus signals adaptor molecules to bind to them (dimerizes)
what do we mean by caspase cascade
positive(?) feedback loop of activated caspase molecules which cleave intracellular molecules leading to death
what type of a signal is apoptotic; how does this affect its control
all-or-nothing (i.e. irreversible); tightly controlled and regulated through Bcl2 proteins
describe Bcl2 family of proteins
promoters or inhibitors of cell death
what Bcl2 proteins promote cell death; inhibit?
Bax and bak; Bcl2 protein
draw out the process of Bax or Bak molecules promoting cell death
main points: apoptotic stimulus on organelle (e.g. mitochondria), bax/bak will facilitate cytochrome c movement from organelle to cytosol, adaptor proteins bind to cytochrome c molecules, these units arrange into a wheel-like structure (apoptosome), procaspase molecules will attach to apoptosome and activate leading to caspase cascade and apoptosis
how can Bcl2 affect bax/bak from promoting cell death
Bcl2 would inhibit Bax/bak from following through with their role
how does unicellular organism growth regulate
thru nutrient availability
how are multicellular organism cells regulated
by extracellular signal molecules for survival, growth, division
what are some examples of extracellular signal molecules that regulate multicellular organism cells
- soluble proteins secreted by neighboring cells
- proteins bound to surface of neighboring cells
what are the positive extracellular signal proteins
- survival factors
- mitogens
- growth factors
what do we mean by positive extracellular signal proteins
things that tell a cell to not go thru apoptosis
define mitogens
- proteins that induce cellular division or
- enhance rate of division
why do animal cells need survival factors
to prevent apoptosis
what are target cells
cells that are beyond synapse of nerve cells
how are survival factors used to avoid apoptosis (EX w nerve cells)
target cells release survival factors to nerve cells; cells that don’t receive survival factors will go thru apoptosis
what is the benefit of survival factors
target cells and survived cells match in number
what are survival factors capable of suppressing and how
apoptosis by regulating Bcl2 family proteins
draw out one way how survival factors can block apoptosis thru regulation of Bcl2 family proteins
main points: survival factor attaches to receptor and activates it; leads to signal transduction pathway that activates transcription factors, which begins transcription of Bcl2 gene; this makes the Bcl2 protein which blocks apoptosis
what are the two overall results that survival factor mechanisms can lead to
- activation of proteins which inhibit apoptosis
- inhibition of proteins that promote apoptosis
what do mitogen stimulate
cellular division
draw out one pathway of how can mitogens work
main points: in a resting cell, mitogen receptor and transcription regulator are inactivated due to an active protein brake; the mitogen attaches to receptor leading to intracellular signaling pathway causing activated cdks; cdks will phosphorylate protein brake and inactivate it; transcription regulator activates and allows for transcription of genes for entry into s phase
what was one of the first mitogens identified
platelet-derived growth factors
what is the role of pdgf in the body, why?
- cell division/proliferation
- blood clotting at wound site triggers platelets to release pdgf, which binds to receptor tyrosine kinases on surviving cells around wound
- if liver is damaged then liver makes hepatocyte growth factor also leading to cell division
how are cells able to grow to completely different sizes
thru growth factor extracellular signals
cell growth and cell cycle control are _______ to e/o
independent
draw a generic pathway of growth factors stimulating cellular growth
main points: GF binds to receptor causing an intracellular pathway, either leading to increase in protein synthesis or decrease in protein degradation; results in cell growth
what is myostatin
a type of inhibitory extracellular signal protein that limits cell growth and proliferation
define myoblasts
skeletal muscle cells
how does myostatin affect myoblast growth and proliferation
by acting as a brake on skeletal muscle formation
what were to happen if the myostatin gene is deleted/mutated
large and bulky skeletal muscles; larger overall organism size
compare mitosis and cytokinesis
separation of chromosomes vs cytosol
how many chromosomes do humans have normally; temporarily during cell cycle
46; 92
if precise separation of chromosomes does not occur then what will happen to the cell
lack of full-functions
what are sister chromatids
duplicated/identical chromosomes during M phase of mitosis
how are sister chromatids held together
cohesin ring protein complexes
if there are defective cohesin rings then, what will happen
major errors in chromosome segregations leading to fatal mutations
all events in M phase are started by
m-cdk
aside from —- what is m-cdk able to trigger ** check what last deck mentioned
chromosome condensation, mitotic spindle assembly
draw out the positive feedback loop of m-cdk accumulation leading to metaphase
main points: inactive m-cdk is dephosphorylated by active phosphatase enzyme which causes m-cdk to become activated. this leads to a positive feedback loop where inactive phosphatase becomes active and helps inactive m-cdk to become active
why is chromosome condensation required
allows for chromosomes to be more easily segregated into dividing cells
what helps DNA to compact in chromosome condensation
protein complexes called condensins (similar structure to cohesin ring)
what mediates mitosis and cytokinesis
cytoskeletal structures (actin, myosin, microtubules)
what aids in physical separation of the chromosomes at the mitotic spindle
microtubules
what aids in the physical separation of the two cells at the contractile ring (cytoplasm)
actin and myosin
draw out how mitotic spindles form over the cell cycle (i.e. draw the centrosome cycle)
main points: initial centrosome (G1) replicates (S/G2); formation of aster and their migration to opposite pole ends (M); mitotic spindles form with replicated chromosomes (M); division of cells with eventual degradation of asters
define an aster
divided chromosomes with microtubules sprouting out
define mitotic spindle
two asters on opposing pole ends of cell with microtubules sprouting out
what are the stages of nuclear (N) and cytoplasmic (C) division (M phase)
- prophase (N)
- prometaphase (N)
- metaphase (N)
- anaphase (N)
- telophase (N)
- cytokinesis (C)
what occurs in prophase
- chromosome condensation
- mitotic spindle assembly (thru addition and removal of tubulin subunits by centrosomes/asters)
what occurs in prometaphase
nuclear envelope breaks and this allows for spindle microtubules to bind chromosomes
what occurs in metaphase
- mitotic spindle gathers and aligns the chromosomes at the spindle centre (cell equator)
- microtubules shrink
what occurs in anaphase
sister chromatids separate from one another and move to opposite poles of cell
what occurs in telophase
- mitotic spindle disassembles
- reassembly of two new nuclear envelopes
- chromosomes decondense to normal interphase size
what occurs in cytokinesis
cell separation by pinching of the cytoplasm
describe interpolar microtubules; in what stage of M phase can we find these in
- the microtubules from opposite polar centrosomes touching one another;
- prophase
microtubules are referred to as dynamically instable; however, there is a point during prophase where they gain stability. what instance is this referring to
interaction (physical touching) of microtubules from one centrosome to another (collective aster), which helps them to align at the cell equator
what is a centromere
specialized DNA region needed for chromosome separation, generally more towards the centre of the cell but can be between the two telomeres of the chromosome
what is a kinetochore
specialized protein complexes that attach to mitotic spindle
what happens to kinetochores during prophase
proteins assemble into large complex on each centromere facing in opposite directions
label a chromosome with the following terms: cohesins, kinetochore, centromere, sister chromatid, non-sister chromatid, telomere, mitotic spindle microtubules
…
why are the chromosomes in the nucleus and why can’t the mitotic spindles access them in prophase
nuclear envelope is not broken down at this point
define bi-orientation
chromosomal orientation to opposite poles of the bipolar spindle before cell division
why do the spindle microtubules “bump into” chromosomes in prometaphase
the nuclear envelope has been disassembled
what happens to kinetochore microtubules during prometaphase
since there are 2 kinetochores on the entire replicated chromosome (1 per sister chromatid), the microtubules for each kinetochore will link to one spindle pole (opposite) – biorientation
why is tension required at the kinetochore
to act as a checkpoint for the cell cycle
what are the classes of microtubules that make up the mitotic spindle
- aster
- kinetochore
- interpolar
describe aster microtubules
microtubules emanating from the aster but are not attached to the microtubules from the opposite aster or chromosomes
describe kinetochore microtubules
microtubules (20-40) emanating from asters that bump into and attach to chromosomes
describe interpolar microtubules
microtubules that link up two polar sides, forming a stable region in middle
the sister chromatids constantly oscillated and adjusted during metaphase, so how do they align at the middle of the cell
microtubules that are attached to the chromosomes are still going thru constant growth and shrinkage and the net result is to lie in the middle
how are kinetochores separated in anaphase
cohesin rings are broken by separase (cohesin proteolysis)
what is separase
- aka separin
- cysteine protease enzyme that hydrolyses cohesin
draw out the pathway of separase cleaving cohesins during anaphase
main points: inhibtory protein (securin) attached to inactive proteolytic enzyme (separase); active anaphase promoting complex ubiquitylates and degrades inhibitory protein making proteolytic enzyme active; proteolytic enzyme cleaves and dissociates cohesins present (in metaphase) during anaphase
APC degrades the inhibitory protein limiting anaphase (ex securin) but can also degrade
M-cyclin
describe the checkpoint for spindle assembly; what is its importance
- chromosomes without microtubule attachment send out a stop signal
- stop signal blocks APC activation
- hence no chromosomal separation until all sister chromatids are attached with kinetochore microtubules under tension
- even one unattached chromosome will result in mutant cells
what are the processes of anaphase
anaphase a and anaphase b
describe anaphase a
- kinetochore microtubules shorten rapidly
- physical poles are moving apart
- both result in chromosomes pulled towards poles
describe anaphase b
- poles pushed toward centre via sliding fence mechanism generated b/w interpolar microtubules
- poles pulled apart
- microtubules growth at plus end of polar microtubules
telophase is often described as the _____ period
restoration
what happens in telophase that triggers cytokinesis(?)
nuclear proteins enter thru nuclear pores of envelope, causing swelling
why can’t chromosomes complete gene transcription during mitosis
due to extreme condensity
draw out nuclear envelope cycle
main points: interphase nuclear pore proteins and lamins phosphorylate; prometaphase nuclear pore proteins and lamins dephosphorylate; fusion of nuclear envelope vesicles
what is the mechanism of nuclear envelope cycle control
(de)phosphorylation of nuclear pore proteins and lamins
what is the first sign of cytokinesis 1 (during anaphase 1)
furrowing of plasma membrane (indentation along middle) due to contractile ring under plasma ring
in reference to the mitotic spindles, cleavage furrow always orients in what direction; why?
- perpendicular
- to ensure one pole is in each daughter cell
describe cytokinesis 2
- actin and myosin filaments overlap
- sliding filaments generate force (similar to skeletal muscle)
- contractile ring disassembles after cell division
