Cytoskeleton: Structure, Types, and Cell Mechanics in Biology

cytoskeleton

a complex network of interlinking filaments and tubules that extend throughout the cytoplasm of a cell

1. spatial organization of the contents of a cell

2. connects the components of the cell both physically and biochemically to the external environment

3. generated coordinated forces that enable the cell to move and/or change shape

functions of the cytoskeleton

fixed; structure

cytoskeleton is not __, but instead is a highly dynamic ___

microfilaments, microtubules, intermediate filaments

three main types of polymers

microfilaments

highly organized network of polymers and actin binding proteins, responds to local signaling activity, length = 13 micrometers, polarized polymers, myosin motor proteins

microtubules

tubulin, long tubes interacting with associated proteins, length = 5000 micrometers, dynamic instability, organized by center centers (MTOC), polarized polymers, dynein and kinesin protein motors

intermediate filaments

family of related proteins that function mainly in strengthening the cytoskeleton, length = 0.5 micrometers, respond to mechanical stress on cell, non-polarized polymers, cannot support molecular motors

cortex

crosslinked, contractile networks

stress fibers

antiparallel contractile structures

lamellipodia

branched and crosslinked networks

filapodia

parallel and crosslinked networks

elastic

"shock absorbers"

contractile

"springs"

actin

highly conserved, ATPase, spontaneous

critical concentration

concentration of subunits at which the filament will neither grow nor shrink

treadmilling

phenomenon when one end of a filament grows in length while the other end shrinks, resulting in a section of filament seemingly "moving" across a stratum or the cytosol

formins

formin; profilin, g-actin

g-actin; profilin

tip-nucleation model

1. __ functions as dimers and interact with the terminal actin subunits

2. each __ monomer binds to a __ unite attached to a __ monomer

3. monomers of __ released from __ are added to growing end of filament

arp2/3 complex

nucleation promotion factors; g-actin

g-actin

arp2/3 mediated model

1. ___ binds to sides or (-) end of actin filaments

2. ___ deliver ___ subunits to the anchored complex

3. ___ monomers are added to (+) end of growing filament

actin architecture

lamellipodia, filopodia, stress fibers, actin cortex

primer

short actin filament that recruits Arp2/3 to existing microfilaments

capping proteins

bind to the end of actin filaments to prevent further extension

alpha-actinin, fimbrin, fascin

cross-linking proteins

ena/VASP

anti-capping proteins

Ca2+

cofactor, blocks polymerization

Mg2+

cofactor, promotes polymerization

myosin motors

act as active "springs" for the contractile unite

arp2/3

actin filaments are not nucleated by __

nucleation or assembly

crosslinking proteins play no role in ___ or ___

identifying quality

the distance between filaments linked together

CLANs

crosse-linked actin networks

increased elasticity

crosslinked actin networks will adjust to outside stress applied to the cell resulting in __

persistent severing

low adf/cofilin

rapid binding and eventual severing

high adf/cofilin

severing

adf/cofilin

debranching

adf/cofilin, GMF

myosin induced disassembly

directed motion of myosin can induce filament buckling and eventually breakage when one end of the myofilament moves faster than the other one

lamllipodia

the projection on the leading edge of the cell that propels the cell across a substrate

filopodia

projections extending beyond the leading of the cell thought to be involved in changes to cell direction

stress fibers and transverse arcs

contractile fibers throughout the cell consisting of unbranched actin filaments and myosin

cell cortex

a thin contractile actin shell containing myosin in its network, underlying the inner face of the plasma membrane

invadopodia

tiny footlike protrusions called ___ enable highly metastatic cancer cells to invade neighboring tissues

cofilin; spatially associated; cofilin; tau pathology

__ rods/aggregates were ___ with neuritic plaques. The researchers concluded that the ___ rods/aggregates makes a sequence of events that correlates with the development of ___ and AD independent of patient age

microtubles

reversible self-assembly of tubulin in buffers containing Ca2+ chelators and GTP

colchincine

microtubular inhibitor

tubulin, Ca2+, GTP

when present in a buffer system, spontaneously make microtubules

oosawa

classical polymerization theory

beta-tubulin

can hydrolyze GTP to GDP

alpha-tubulin

GTP bound and cannot hydrolyze

alpha and beta

two types of tubulin

hydrophobic interactions

intra-pt contacts, beta to alpha

hydrophilic interactions

inter-pt contacts, beta to beta, alpha to alpha

dynamic instability

co-existence of growing and shrinking microtubules in the same conditions

rescue

type of dynamic instability, the transition from shrinkage to growth, presence of GTP islands along the prototubule

catastophe

type of dynamic instability, the transition from growth to shrinkage, aging behavior, MT-Lattice defects

katanin, spastin, fidgetin

microtubule severing enzymes

microtubule organizing center (MTOC)

structure in eukaryotic cells from which the microtubule array emerges

centriole pair

make up the centrosome

basal bodies

cilia and flagella

centrioles

mitotic and meiotic cells

gamma

type of tubulin inside of centrioles

2 gamma tubulin and proteins

gamma-tubulin small complex

6 small gamma-tubulin complexes and 1/2 of one

gamma-tubulin ring complex

augmin complex

non-centrosome attachment factors

microtubule associating proteins (MAPs)

proteins that interact with the microtubules of the cellular cytoskeleton

class 1

MAPs that promote the assembly of microtubules, 2 types (Type I - MAP1 proteins, type II - MAP2 proteins and tau)

class 2

MAPs that "destabilize" microtubules (MCAK, EB1, or kinesin 8)

tau hypothesis

states that excessive or abnormal phosphorylation of tau results in the transformation of normal adult tau into PHF-tau (paired helical filament) and NFTs

axoneme

two central microtubules

A tubules

complete MT with 13 prototubules

B tubules

only 10 prototubules

cilia and flagella

move in a dynein dependent fashion by sliding of the microtubules inside the axoneme

intermediate filaments

large family of conserved cytoskeletal proteins that establish the third major filament system in the cell

keratin

protein that protects the epithelial cells from damage and stress (class I - acidic, alpha keratins, class II - basic, beta keratins)

neurofilament proteins

major component of the neuronal cytoskeleton, and are believed to function primarily to provide structural support for the axon and to regulate axon diameter

nuclear lamins

major components of a filamentous layer, the nuclear lamina, that is closely associated with the inner nuclear membrane

spectraplakins (plectin)

are linker proteins that integrate MT, MF, and IFs

motility

movement of a cell or organism through the environment, movement of the environment past or through a cell, movement of components in the cell

contractility

used to describe shortening of muscle cells

microfilament-based contractility and microtubule-based motility

two major motility systems in eukaryotes

head domain

globular heavy chains containing actin binding and ATP binding domains

hinge domain

consists of two or more light chains which regulate the ATPase activity of the motor

tail domain

varies among myosin family members and confers the ability to bind to various cargoes as well as other myosin molecules

thick filaments

composed of myosin (multiple proteins fused together)

thin filaments

composed of F-actin, tropomyosin, and troponin

alpha-actinin

keeps actin filaments bundled into parallel arrays

capZ

maintains attachment of (+) actin ends to the Z line

tropomodulin

binds (-) actin ends to prevent unraveling

nebulin

stabilizes actin filament

myomesin

present in H zone and bundles myosin thick filament

titin

attaches thick filaments to Z line and keeps them in the correct position during contraction

transient cross-bridges

regions of overlap between thin and thick filaments are always characterized by the presence of __

cross-bridges

form and dissociate rapidly