5 - Cytoskeleton

3 major cytoskeleton elements

intermediate filaments, microtubules, actin

intermediate filaments

• intermediate in size (10 nm diameter)

• stretch through cytoplasm & across cell to distribute mechanical stress

• forms nuclear lamina (meshwork beneath inner nuclear membrane)

• flexible

• deform under stress but don’t break

microtubules

• larger (25 nm diameter)

• long, straight filaments with some flexibility

• can break under tensile stress

• polarized cytoskeleton filaments w/ + and - ends

  • grow at minus ends from centrosome

microfilaments

• flexible, 7 nm diameter

• highly concentrated at cell cortex

classes of intermediate filaments

• cytoplasmic

  • keratin filaments

  • vimentin filaments

  • neurofilaments

• nuclear

  • nuclear lamins

keratin filaments

intermediate filaments that link adjacent cells

cadherin

mark cell boundaries

desmosomes

filaments in each cell are connected to those of neighbors to provide mechanical strength

human mutations in keratin —> skin blistering

• affect structural integrity of cells in basal layer of epidermis

• causes cells to rupture btwn nucleus & hemidesmosomes that connect cells to basal lamina

lamin filaments

intermediate filaments that line inner face of nuclear envelope to provide attachment sites for chromosomes

linker proteins

connect cytoskeleton filaments and bridge the nuclear envelope and nuclear lamina

mutations in lamin A —> progeria

• disrupt the uniform nuclear lamina inside the nuclear envelope

• results in structural defects —> progeria

• children show advanced aging early in life

protofilaments

repeating subunits of aB-tubulin heterodimers which are arranged with the same orientation (gives polarity)

dynamic instability in microtubules

they grow and shrink depending on intrinsic properties and extrinsic factors

capping proteins (microtubules)

stabilize plus ends of microtubules and bias assembly towards specific areas

GTP hydrolysis in dynamic instability

• both a & B tubulin bind GTP but only B can hydrolyze GTP to GDP

• microtubules stabilized by GTP cap at plus end

• tubulin carrying GTP bind more tightly to one another than ones carrying GDP

• GTP cap lost as B tubulin hydrolyzes GTP to GDP when growth slows

• When rate of GTP hydrolysis exceeds addition of new GTP tubulin heterodimers, protofilaments curl back and peel away

motor proteins

• kinesin motors walk towards plus end of microtubules

• dynein walks towards minus end

• dimerize through their stalk domains

• each dimer has two globular heads that interact with microtubules and a tail domain