CYTOSKELETON Flashcards
families of protein filaments
actin filaments, microtubules, intermediate filaments
shape of the cell’s surface; whole-cell locomotion; pinching of one cell into two
actin filaments
positions of membrane-enclosed organelles; direct intracellular transport; from the mitotic spindle during cell division
microtubules
mechanical strength; protective cage for the cell’s DNA; form tough appendages (hair and fingernails)
intermediate filaments
cell-surface projections class of actin filaments
lamellipodia and filopodia
motile whips or sensory devices of cells
cilia
belt around the middle of the cell; pinches the cell into two identical sister cells
contractile ring
protrusive structure filled with newly polymerized actin filaments
neutrophils
specialized epithelial cells in the intestines and lungs
microvilli and cilia
present in the apical surface and the basolateral surface; maintain strong adhesive contacts with one another to enable this single layer of cells to serve as an effective physical barrier
polarized epithelial cells
actin filaments are made of ________ using ATP hydrolysis
actin subunits
microtubules are made from clusters of _________ through __________ hydrolysis
tubulin subunits, GTP
polarized structural proteins; asymmetrical form; polarized
actin filaments and microtubules subunits
determine the spatial distribution and the dynamic behavior of the filaments; bind to the filaments or their subunits to determine the sites of assembly of new filaments
accessory proteins
bind to a polarized cytoskeletal filament; energy from ATP hydrolysis to move along the filament, and the “cargo” they carry
motor proteins
tubulin homolog; generate a bending force that drives the membrane invagination and site for localization of enzymes
FtsZ
actin homolog; scaffold to direct the synthesis of the peptidoglycan cell wall
MreB and Mbl
abnormalities in cell shape and defects in chromosomes segregation
mutations
bacterial actin homolog; encoded by a gene on certain bacterial plasmids that also carry genes responsible for antibiotic resistance
ParM
homolog of intermediate filaments
Caulobacter crescentus – crescentin
structural proteins present in muscle cells
α-Actin
almost non-muscle cells
β- and γ-actins
faster-growing; barbed end
plus end
pointed end; slower-growing
minus end
the minimum length at which random thermal fluctuations are likely to cause it to bend
persistence length
assembly of actin subunits
head-to-tail → tight, subunits right-handed helix
assemble into an initial aggregate, or nucleus, that is stabilized by multiple subunit–subunit contacts and can then elongate rapidly by addition of more subunits
nucleation
G-actin proceeds in three sequential phases:
nucleation, elongation, steady-state
rapidly increases in length by the addition of actin monomers to both of its ends
elongation
G-actin monomers exchange with subunits at the filament ends, but there is no net change in the total mass of filaments
steady-state
when steady-state phase has been reached, the concentration of the pool of unassembled subunits is called
critical concentration, Cc
the ratio of the “on” and “off” rate constant; measures the concentration of G-actin where the addition of subunits is balanced by the dissociation of subunits
dissociation constant
manifested by the different rates at which G-actin adds to the two ends
polarity of F-actin
difference in elongation rates at the opposite ends of an actin filament is caused by a ______________________at the two ends
difference in Cc values
actin can only elongate in the _________
minus end
actin can only elongate in the __________ when the minus end is blocked
plus end
G-actin concentration below Cc+, there is:
no filament growth
G-actin concentrations between Cc+ and Cc-
growth is only at the (+) end
G-actin concentration above
no growth at both ends
G-actin concentrations intermediate between the Cc values for the (+) and the (-) ends, subunits continue to be added at the (+) end and lost from the (-) end
steady-state phase
newly added subunits traveling through the filament, as if on a
treadmill
actin behavior is regulated by _____________ that bind actin monomers or filaments
accessory proteins
a measure of how long an individual actin monomer spends in a filament as it treadmills
filament half-life
inhibition of actin polymerization; they cannot associated with either the plus or minus ends; neither hydrolyze nor exchange their bound nucleotide
thymosin
binds to the face of the actin monomer opposite the ATP-binding cleft, blocking the side of the monomer that would normally associate with the filament minus end, while leaving exposed the site on the monomer that binds to the plus end
profilin
prerequisite for cellular actin polymerization
filament nucleation
actin-related proteins; nucleates actin filament growth from the minus end, allowing rapid elongation at the plus end
Arp 2/3 complex
dimeric proteins that nucleate the growth of straight, unbranched filaments that can be cross-linked by other proteins to form parallel bundles
formins
Formin-dependent actin filament growth is strongly enhanced by the association of actin monomers with
profilin
side-binding proteins; elongated protein that binds simultaneously to six or seven adjacent actin subunits
tropomyosin
binds at the plus end; stabilizes an actin filament (inactive)
capping protein (CapZ)
capping long-lived actin filaments in muscle; minus end-binding; binds tightly to the minus ends that have been coated and stabilized by tropomyosin
tropomodulin
coats the filament completely and present in high amounts
side-binding
affect filament dynamics
end-binding
proteins that break an actin filament into many smaller filaments; generating new filament ends
severing proteins
activated by high levels of cytosolic Ca2+; interacts with the side of the actin filament and contains subdomains that bind to two different sites
gelsolin superfamily
actin depolymerizing factor; binds along the length of the actin filament, forcing the filament to twist a little more tightly
cofilin
actin filament types of arrays
dendritic networks, bundles networks, weblike (gel-like) networks
made of the long, straight filaments produced by formins
bundles networks
Arp 2/3 complex
dendritic networks
diff. actin networks depends on:
specialized accessory proteins
cross-link actin filaments into parallel array
bundling proteins
hold two actin filaments together at a large angle to each other, forming a looser meshwork
gel-forming proteins
enable stress fiber and other contractile arrays to contract
myosin II
close packing of actin filaments; not contractile
fimbrin
cross-links oppositely polarized actin filaments into loose bundle; allowing the binding of myosin and formation of contractile actin bundles
α-actinin
formation of a loose and highly viscous gel; by clamping together two actin filaments roughly at right angles; form actin filament webs or gels
filamin
cytoskeletal protein actin projection on the leading edge of the cell; determines cell movement direction by protrusive force that arises from the actin network
lamellipodia
defect in nerve-cell migration during early embryonic development
filamin A gene mutations
periventricular region of the brain fail to migrate to the cortex and instead form nodules
periventricular heterotopia
web-forming; long, flexible protein made out of four elongated polypeptide chains; allows RBC to “spring back” to shape
spectrin
first motor protein identified; generates force for muscle contraction
myosin
an elongated protein formed from two heavy chains and two copies of each light chains
myosin II
globular head domain at its N-terminus; contains force-generating machine
heavy chain
bind close to the N-terminal head of myosin
light chains
MYOSIN: SLIDING FILAMENT THEORY
- myosin head binds and hydrolyzes ATP
- it then uses the energy from ATP hydrolysis to walk toward the plus end of an actin filament
[opposing orientation of the heads makes the filament efficient at sliding] - ATP-driven sliding of actin filaments results in a powerful contraction
each step of the movement along actin is generated by the swinging of an:
8.5nm long α-helix – lever arm
a piston-like helix that connects movements at the ATP-binding cleft in the head to small rotations
converter domain
changes in the conformation of the myosin are coupled to changes in its:
binding affinity for actin
a cylindrical structure 1-2 μm in diameter that is often as long as the muscle cell itself
myofibril
myofibrils is made up of a long, repeated chain of tiny contractile units called _________, which gives the vertebrate myofibril its striated appearance
sarcomeres
parallel and partly overlapping thin and thick filaments
sarcomeres
myosin filaments sliding past the actin thin filaments, with no change in the
length of either type of filament causes:
sarcomere shortening
initiates muscle contraction; signal passes to the skeletal muscle from the nerve that stimulates it
rise in cytosolic Ca2+
two major features of the muscle cell make extremely rapid contraction possible
- myosin motor heads coupled binding and hydrolysis to ATP
- a specialized membrane system relays the incoming signal rapidly throughout the entire cell
MUSCLE MOVEMENT: Ca+ Signaling
- signal from the nerves triggers an action potential that signals the T tubules (transverse tubules)
- T tubules conducts the action potential to the sarcoplasmic reticulum which triggers the release of Ca2+ channels in the sarcoplasmic reticulum
- Ca2+ flooding into the cytosol then initiates the contraction
elongated protein that binds along the groove of the actin filament helix
tropomyosin
complex of three polypeptides (T, I, & C)
troponin
elevated intracellular Ca2+ levels regulate contraction by a mechanism that depends on:
calmodulin
induces the phosphorylation of smooth muscle myosin on one of its two light chains; activated by Ca2+-bound calmodulin
myosin light-chain kinase (MLCK)
common cause of sudden death in young athletes; heart enlargement, abnormally small coronary vessels, disturbances in heart rhythm
familial hypertrophic cardiomyopathy
minor missense mutations in the cardiac actin gene
dilated cardiomyopathy
distinct myosin families
37
human genome includes ___ myosin genes
40
intracellular organization; microvilli and endocytosis
myosin I
two-headed myosin with a large step size; organelle transport along actin filaments; move progressively along actin filaments without letting go
myosin V
actin cables in the mother cell point toward the bud, where actin is found in patches that concentrate where cell wall growth is taking place
Saccharomyces cerevisiae
highly dynamic and play comparably diverse and important roles in the cell; polymers of tubulin
MICROTUBULES
longitudinal axis - “top” of β-tubulin molecule forms an interface with the “bottom” of the α-tubulin molecule in the adjacent heterodimer; lateral
contacts, α–α and β–β
protein-protein contact
microtubules dynamics is influenced by the:
hydrolysis of GTP
GTP hydrolysis occurs only within
β-tubulin
bound GTP
T form
bound GDP
D form
GTP tubulin tends to ________, and GDP-tubulin to ____________
polymerize, depolymerize
high rate of addition – the tip of the polymer remains in the T form
GTP cap
rapid interconversion between a growing and shrinking state
dynamic instability
growth to shrinkage
catastrophe
shrinkage to growth
rescue
tubulins subunits with GTP bound to the β-monomer produce __________ that make strong and regular lateral contacts with one another
straight protofilaments
associated with subtle conformational change in the protein - curved
hydrolysis of GTP to GDP
constrain the curvature of the protofilaments, the ends appear straight; terminal subunits have hydrolyzed, constrains is removed, spring apart
GTP cap
microtubules functions are inhibited by both:
polymer-stabilizing and polymer destabilizing drugs
causes microtubule depolymerization
colchicine and nocodazole
binds to and stabilized microtubules; increase in tubulin polymerization; used to treat cancers of the breast and lung
taxol
microtubule-depolymerizing and polymerizing drugs preferentially
kill dividing cells
smaller amounts, involved in the nucleation of microtubule growth
γ-tubulin
where specific intracellular location microtubules nucleation occurs
microtubule-organizing center (MTOC)
two accessory proteins bind directly to the γtubulin, along with several other proteins that help create a spiral ring of γ-tubulin molecules, which serves as a template that creates a microtubule with 13 protofilaments
γ-tubulin ring complex (γ-TuRC)
well-defined MTOC; located near the nucleus
centrosome
embedded in the centrosome; a pair of cylindrical structures arranged at right angles in an L-shaped configuration; barrel shape with striking nine-fold symmetry
centrioles
where microtubule nucleation takes place
pericentriolar material
MTOC embedded in the nuclear envelope found in budding yeast, fungi, and diatoms; no centrioles in fungi or plants; use γ-tubulin to nucleate their
microtubules
spindle pole body
dynamic plus ends pointing outward toward the cell periphery and stable minus ends collected near the nucleus
aster-like configuration
proteins that bind to microtubules; stabilize against disassembly; mediate interactions with other cell components – prominent in neurons, axons and dendrites that extend from the cell body
microtubule-associated proteins (MAPs)
long projecting domain; form bundles of stable microtubules that are widely spaced
MAP2
shorter projecting domain, form bundles of more closely packed microtubules
tau
bind to microtubule ends and appear to pry protofilaments apart
catastrophe factors (kinesin-13)
protects microtubule minus ends from the effects of catastrophe factors
Nezha / Patronin
enriched at microtubule plus ends; binds free tubulin subunits and delivers them to the plus end; promoting microtubule polymerization and simultaneously counteracting catastrophe factor activity
XMAP215
stabilized by association with a capping protein or the centrosome; depolymerization sites
minus ends
explore and probe the entire cell space
plus ends
accumulate at these active ends (+) and appear to rocket around the cells as passengers at the ends of rapidly growing microtubules; dissociating from the ends when microtubules shrink
plus-end tracking proteins (+TIPs)
modulate the growth and shrinkage of microtubule; control microtubule positioning
kinesin-related catastrophe factors and XMAP215
small dimeric proteins; attach to the plus end; allow the cell to harness the energy of polymerization; used for positioning the spindle, chromosomes, or organelles
EB1
unpolymerized tubulin subunits to maintain a pool of active subunits
cell sequester
binds to two tubulin heterodimers and prevents their addition to the ends of microtubules; decrease the effective concentration of tubulin subunits
stathmin (Op18)
“sword”; made up for two subunits, smaller ones hydrolyze ATP performs the actual severing, larger on directs katanin to the centrosome
katanin
two types of motor proteins:
kinesins and dyneins
carriers membrane-enclosed organelles away from the cell body toward the axon terminal by walking toward the plus end of microtubule
kinesin-1 (“conventional kinesin”)
distinct families in kinesin superfamily
14
depolymerize microtubule ends
ATP hydrolysis
minus-end directed motors; one, two, or three heavy chains and large and variable number of associated intermediate, light-intermediate, and light
chains
dyneins
homodimers of two heavy chains
cytoplasmic dyneins
organelle and mRNA trafficking, for positioning the centrosome and nucleus during cell migration, construction of the microtubule spindle
cytoplasmic dynein I
cilia, transport material from the tip to the base of the cilia
cytoplasmic dynein II
highly specialized for the rapid and efficient sliding movements of microtubules that drive the beating of cilia and flagella; largest of the known molecular motors;
fastest
axonemal dyneins (ciliary dyneins)
responsible for fast antegrade axonal transport → movements toward the cell’s periphery
kinesin
retrograde axonal transport → movement towards the cell center
cytoplasmic dynein
large protein complex associated to cytoplasmic dynein; to translocate organelles
effectively
dynactin
cells fail to migrate to the cerebral cortex of the developing brain
smooth brain (lissencephaly)
a dynein-binding protein, required for nuclear migration in several species
Lis1
contain large pigment granules that can alter their location in response to neuronal or hormonal stimulation
fish melanocytes
assembly depends on reorganization of the interphase array of microtubules to form bipolar array of microtubules
mitotic spindle
receive signals; mixed polarities of microtubules
dendrites
transmit signals; minus end pointing back toward the cell body, the plus end pointing toward the axon terminals
axons
highly specialized and efficient motility structures built from microtubules and dynein
cilia and flagella
found on sperm and many protozoa; undulating motion, they enable the cells to which they are attached to swim through liquid media
flagella
cell organelle which beats with a whip-like motion that resembles the breaststroke in swimming
cilia
cell movement is produced by the bending of its core, which is called the
axoneme
form bridges between the neighboring doublet microtubules around the circumference of the axoneme
axonemal dynein
hereditary defects in axonemal dynein causes -
ciliary dyskinesia or Kartagener’s syndrome
bacterial flagella
flagellin
nonmotile counterpart of cilia and flagella; specialized cellular compartments or organelles; shares structural features with motile cilia
primary cilium
nine groups of fused fused triplet microtubules arranged in a cartwheel
centriole
converting light to neural signal
rod and cone cells of retina
odorant reception and signal amplification
nasal epithelium
forms a cytoplasmic filament ; cells that are subject to mechanical stress
INTERMEDIATE FILAMENTS
made up of an equal mixture of type I (acidic) and type II (neutral/basic) keratin proteins → heterodimer
keratin filament
epithelial cancers
carcinomas
cell-cell contact
desmosomes
cell-matrix contact
hemidesmosomes
defective keratins in the basal cell layer of the epidermis
epidermolysis bullosa complex
intermediate filaments found in high concentrations along axons
neurofilaments
influences how fast electrical signals travel down the axon; influenced by neurofilament gene expression
axonal diameter
ALS, or Lou Gehrig’s disease
amyotrophic lateral sclerosis
expressed in skeletal, cardiac, and smooth muscle, where it forms a scaffold around the Z disc of the sarcomere
Desmin
stabilize microtubules against depolymerization
vimentin-like filaments
scaffolds for proteins that control myriad cellular processes including transcription, chromatin organization, and signal transduction
A-type lamins
associated with mutant versions of lamin A and include tissue-specific diseases
laminopathies
The intermediate filament network is linked to the rest of the cytoskeleton by members of a family of proteins called
plakins
large and modular, containing multiple domains that connect cytoskeletal filaments to each other and to junctional complexes
plectin
additional filament system; forms ring and cage-like structures; act as scaffolds to compartmentalize membranes into distinct domains
septins
septin genes in humans
13
relies on the coordinated deployment of the components and processes
cell migration
bone cells that migrate through connective tissues
fibroblast
cells responsible for bone remodeling and renewal
osteoclasts
plasma membrane is pushed out at the front of the cell; relies on forces generated by
actin polymerization
protrusion
actin cytoskeleton connects across the plasma membrane to the substratum
attachment
the bulk of the trailing cytoplasm is drawn forward
traction
formed by migrating growth cones of neurons and some type of fibroblast; one-dimensional; contain a core of long, bundled actin filaments
filopodia
formed by epithelial cells and fibroblast; two-dimensional sheet-like structures; contain a cross-linked mesh of actin filaments
lamellipodia
actin-rich protrusion; three-dimensional; important for cells to cross tissue barriers
invadopodia and podosomes
depends on hydrostatic pressure within the cell; generated by the contraction of actin and myosin
blebbing
abundant keratin filaments; epithelial cells of the epidermis of fish and frogs
keratocytes
assembling at the front and disassembling at the back
treadmilling
binds preferentially to actin filaments containing ADP-actin; new T-form filaments generated at the leading edge resistant to depolymerization
cofilin
dynamic assemblies of structural and signaling proteins
focal adhesions
disengaged interaction between actin network and focal adhesions, polymerization pressure at the leading edge and myosin-dependent contraction cause the actin network to slip back
retrograde-flow
the front end of the cell remain structurally and functionally distinct from the back end
cell migration
cytoskeletal coordination takes the form of the establishment of
cell polarity
activated Cdc42
WASp proteins family
severe form of immunodeficiency in which immune systems cells have abnormal
actin-based motility and platelets do not form normally
Wiskott-Aldrich Syndrome
activates the WASp family members; activates the cross-linking activity of the gel-forming protein filamin and inhibits the contractile activity of the motor protein myosin II
Rac-GTP
turns on formin proteins to construct parallel actin bundles; activates a protein kinase that in indirectly inhibits the activity of cofilin, leading to actin filament stabilization
Rho-GTP
the movement of a cell toward or away from a source of some diffusible chemical
chemotaxis
chemotaxis acts through _________ set up large-scale cell polarity
Rho family proteins
cells that moves toward a source of bacterial infection
neutrophils
two processes directly inhibit each other;
