Cytoskeleton

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Cytoskeleton
cytoskeleton series of proteins that provide
internal support for the cell 3 major types--
microfilaments, intermediate filaments,
microtubules microfilaments 7nm filaments made
of actin polarized, with and - ends
involved in movement and cell shape intermediate
filaments 8-12nm filaments made of different
proteins in different tissues 8 wrapped
filaments and maintains shape and strengthens
cells microtubules 25nm diameter filaments
made of a and b- tubulin required for
motility and organelle movement
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Cytoskeleton
many of the functions of cytoskeleton have been
found using various drugs that block their
function if one of these drugs disrupts a
certain function, that function probably
depends upon that cytoskeleton colchicine drug
that binds to tubulin monomers preventing the
formation of microtubules taxol drug that binds
to microtubules and stabilizes them currently
being tested for anti-cancer activity cytochalasi
n D and latrunculin A drugs that inhibit actin
polymerization phalloidin drug that blocks
depolymerization of actin, stabilizing
microfilaments
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Microtubules
2 different types of microtubules axonemal
microtubules microtubules used in movement-
cilia, flagella, basal bodies axoneme central
microtubule shaft in the appendages with other
bound proteins cytoplasmic microtubules work
inside the cell body found in axons, some
motile cells, and mitotic spindles (moving the
chromosomes during cell division)
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Microtubules
a and b tubulins bind to each other first, and
don't come apart these dimers then bind
together to form a hollow tube of
tubulin protofilament 'filament' or row of
tubulins that make up the microtubule a and b
tubulin are always arranged the same way, giving
it polarity most cells express more than 1
isoform of each tubulin isoform very similar
proteins that serve the same function but have
slightly different amino acid sequences critical
concentration concentration at which tubulin
monomers bind each other and form a tubule
lower concentration at the '' end where the
tubules grow fastest
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Microtubules
nucleation slow process that starts the process
of microtubule growth elongation faster growth
of microtubule after nucleation has started
it plateau point at which subunits are being
added and removed equally
dynamic instability model model which uses GTP
binding to control if tubulin subunits are
added or removed GTP added, GDPremoved
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Microtubules
microtubule organizing center (MTOC) protein
structure in a cell that anchors one end of
the microtubule found in both centrioles
(mitosis) and basal bodies (cilia flagella)
have a protein called g-tubulin, yet another
tubulin subunit serves as a solid base for
microtubules addition/subtraction at other end
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Microtubules
microtubule associated protein (MAP) protein
that binds to microtubules along its length
and regulates the microtubule or uses it for
support motor MAPs protein motors that move
vessicles along microtubules 2 types kinesin
and dynein non-motor MAPs give different
processes different mechanical strength found
mostly in brain, also affects the structure of
the cell axons have a protein called tau
dendrites have a protein called
MAP2 phosphorylation of MAPs regulate their
function for cells to modify microtubules
quickly
axon
dendrites
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Microfilaments
smallest of the cytoskeleton works with myosin
in muscle contraction involved in cell movement
and cleavage furrow during cell division
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Microfilaments
actin protein that makes up microfilaments also
binds ATP G-actin globular actin, or actin
monomer F-actin filamentous actin, or
polymerized actin found in every type of
eukaryotic cell G-actin binds ATP, hydrolyzes to
ADP when it polymerizes to form F-actin to
speed reaction F-actin is composed of 2
polarized filaments 3 different isoforms of
actin a-actin found only in muscle cells b
and g-actin found in other cells enriched
in different parts of the cell different
isoforms of actin from all species form
filaments with each other-- very highly conserved
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Microfilaments
moving cells need to be able to form and dissolve
actin filaments in portions of the cell that
are moving lamellopodia large flattened areas
of cell moving forward filopodia small,
filaments that extend and retract
frequently stress fiber actin bundle linking to
the cell surface polymerization is controlled by
actin binding proteins and ATP bound
G-actin capping proteins bind to the ends of
actin filaments blocking addition and
removal other proteins catalyze addition,
removal or branching
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Microfilament Regulation
innositol phospholipids regulate some capping
functions of actin different phosphorylated
forms can do different things IP3 signaling
molecule in G-protein signaling by
phospholipaseC related molecule PIP2 binds
capping proteins, regulating actin growth Arp
2/3 complex nucleates branching from the side of
an actin filament formins proteins that
regulate actin cables and the contractile
ring Rac small G protein that enhances
lamellopodia formation Rho small G protein that
enhances stress fiber formation Cdc42 small G
protein that enhances filopodia formation these
small G proteins link receptors to changes in the
cytoskeleton and allow chemotaxis (movement in
response to a chemical cue) to occur
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Microfilaments
microfilaments have to interact with one
another cortex dense network of actin filaments
underneat the membrane links various filaments
together to support the cell, and aid
movement filamin protein with 2 actin binding
domains to crosslink microfilaments gelsolin
protein that breaks and then caps microfilaments
regulated by phosphoinositols balance between
filamin, gelsolin, rac, rho, cdc42, PIP2, etc
allows the cell to react and change its shape
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Microfilaments
intestinal cells have microvilli to increase the
surface area of cells to absorb
nutrients microvilli long, thin structures with
a core of bundled actin filaments to increase
surface area 20 fold actin bundles linked to
cell membrane and cortex fimbrin and villin link
actin monomers in bundle spectrin links actin to
membrane proteins ankyrin, ezrin, radixin, etc
are more membrane- actin binding
proteins mutating different proteins affect
different cell functions- change shapes,
signaling, or growth
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Microfilaments
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Intermediate Filaments
intermediate filaments are the least soluble
fibers and are not polarized only found in
multi-cellular organisms and are tissue
specific they are still related to each other,
however, by amino acid sequence generally
provides mechanical strength to cells more
intermediate filaments are in tissues with
mechanical stress plectin protein linking
microfilaments to microtubules plakins family of
proteins linking various cytoskeleton
proteins different types of cytoskeleton work
together to provide support, flexibility, and
a transport system for cells