cytoskeleton II: actin & cell motility Flashcards
microfilaments are
polarized with a plus and minus end
there are two steps in the filament formation:
- nucleation
2. extension
once nucleation is achieved,
extension proceeds rapidly
nucleation occurs from ___ end
minus
why does nucleation not occur spontaneously?
would require very high actin concentration
nucleation is catalyzed by
different proteins that determine the structure of polymerized actin
actin related protein (ARP2/3) nucleation leads to
branched filaments
formin nucleation leads to
parallel bundles
microfilament polymerizes from the
plus end following nucleation
_____ are involved in regulating polymerization and depolymerization
over 60 accessory proteins
profilin binds to
actin and prevents polymerization
capping proteins:
cap the plus or minus end to inhibit polymerization or depolymerization
cap plus end
inhibit polymerization
cap minus end
inhibit depolymerization
cofilin severs
actin filaments and induces depolymerization
Actin in epithelial junctions:
Actin anchors proteins involved in tight junctions and adherens junctions that hold epithelial cells together.
The proteins anchored by actin in adherens junctions are
cadherins and catenins.
Decreased association of actin with the adherens junction proteins leads to
loss of cell-to-cell adhesion.
Loss of cell adhesion increases
cell motility resulting in epithelial-to-mesenchymal transitions, which can cause cancer.
Actin in microvilli on the apical surface of epithelial cells:
Microvilli consist of actin bundles, held together by cross-linking proteins (villin and fimbrin) and attached to the plasma membrane by myosin-I and calmodulin.
Microvilli function to:
increase the surface area of epithelial cells for housing cell transporters
Loss of microvilli in the small intestine leads to
microvilli inclusion disease, which causes intractable diarrhea and dehydration in infants born with the disease.
Molecular motors are proteins that
can transform energy from ATP hydrolysis into motion.
Myosins are
- actin-associated motor proteins.
Myosins are made up of
coiled-coil dimers that polymerize into filaments.
Myosin have two heads that bind to
actin and ATP and a tail that binds to cargo. These molecular motors “walk” along actin towards the plus end with the hydrolysis of bound ATP.
There are three main classes of myosins:
- those involved in cargo transport
- those responsible for muscle contraction
- unconventional myosins.
Myosin-II is the molecular motor protein responsible
for muscle contraction.
Myosin-II is made of a .
coiled-coil complex of myosin filaments
This coiled complex of myosin II forms the
thick filament that “walks” along actin thin filaments during muscle contraction.
Thick filaments have many heads for
binding actin, thus only a small percentage of heads are actin-bound at one time.
transport myosins, which have a ____duty ratio
50:50
(half of the heads are bound at one time).
Myosins I and V are the unconventional myosins that are associated with:
membranes and bind to organelles through their tails
Myosin I and V are responsible for
moving these organelles around the cell along F- actin microfilaments.
Cells commonly translocate by
amoeboid movement.
Amoeboid movement is governed by
changes in the actin cytoskeleton, induced by extracellular signals.
Mechanism of amoeboid locomotion:
- protrusion
- attachment
- traction
- detachment
protrusion:
signaling from RAC and WASp causes F actin to polymerize and form flat projections called lamellipodia
lamellipodia result from
polymerization catalyxes by actin related proteins Arp2/3
filopodia form in
protrusion
filopodia are the result of
polymerization catalyzed by forming and have attached receptors for “sampling” the environment in front of the cell during movement
attachment:
the lamellipodia protrusions attach with the substratum ahead
traction
the cell is pulled forward by tension created by anchored actin protrusions and myosin molecular motors, which slide actin filaments along each other within the cell
detachment
adhesions behind the new site of the anchorage are released to allow for translocation of the cell.
This release is acheived through the depolymerization of action of the protein cofilin
Cell motility is required during
development as undifferentiated cells migrate to their proper location.
Neural crest cells originating from the neural tube must migrate
throughout the body to give rise to pigment cells and cells of the peripheral nervous system.
The actomyosin ring is an
actin ring structure with associated mysoins that forms around a dividing cell.
the actomyosin ring contracts through the
action of the myosin heads and ATP hydrolysis during cytokinesis to separate the daughter cells.
The actomyosin ring is highly
highly regulated, so that the timing of its formation and contraction can give rise to daughter cells of varying symmetry.
The site and timing of contraction of the actomyosin ring regulates the _______
This is important in allowing for _______
symmetry of cell division.
asymmetric cell divisions.
examples of asymmetric cell divisions
- cells giving rise to RBCs divide so that the nucleus is separated from the remainder of the cell
- In platelet formation, a cell duplicates its genetic material before dividing and later divides asymmetrically many times to give rise to many cell fragments
- cells can be left connected by canals by the persistence of the actomyosin ring following division
- The division of epithelial cells through a symmetric vertical axis ensures that cells maintain a monolayer distribution
G actin
globular actin
assembles for form two stranded helical filaments (F-actin)
F actin is made up of
G actin
Microfilaments (MF) are critical for cell
shape
movement
polarity
phalloidin,
extracted from the highly toxic fungus Amanita phalloides (“death cap”), which binds to and stabilizes F-actin (causing a net increase in actin polymerization).
amoeboid movement is important in
- development
- host defense
- cancer
Wiskott-Aldrich syndrome (WAS): inheritance
WAS is a rare, X-linked immunodeficiency disease.
Lissencephaly:
is a
severe defect of brain development resulting in a smooth cortical surface, i.e., the absence gyri
WAS mutation
results from WASp mutations.
WAS clinical symptoms
thrombocytopenia (reduced platelet number and size) and recurrent infections.
WAS macrophages and neutrophil leukocytes have been shown to be
migration- and chemotaxis-deficient.
Lissencephaly : caused by
Loss-of-function of n-cofilin, an actin filament depolymerizing factor, results in lissencephaly and the associated severe mental retardation.
