Cell Bio chp. 17 - Cytoskeleton

Cytoskeleton general functions

• cell support

• transport of organelles and vesicles

• movement

• cell division

• response to environment

where do intermediate filaments expand from and where are they anchored

Expand from center of cell

Anchored at cell membrane

desmosomes

cell junction at plasma membrane that link intermediate filaments of neighboring cells

can intermediate filaments be found in the nucleus

Yes

What is the secondary structure of an intermediate filament monomer

a-helix

dimer structure for intermediate filaments

coiled-coil

tetramer structure of intermediate filaments

staggered antiparallel coiled coils

What can eight intermediate filament tetramers make

helical array that makes up rope like structure and can be added to growing filament

4 major classes of intermediate filaments and location

• keratin filaments (cytoplasm)

• Vimentin and vimentin-related filaments (cytoplasm)

• neurofilaments (cytoplasm)

• nuclear lamins (nucleus)

Most diverse intermediate filament

Keratin filaments

What cells contain keratin filaments

epithelial cells

Cells containing vimentin and vimentin related filaments

• connective tissue cells

• muscle cells

• glial cells

cells containing neurofilaments

nerve cells

cells containing nuclear lamins

all animals cells

(all animal cells have a nucleus so they have nuclear lamins)

Epidermolysis bullosa simplex

Keratin filament mutation that interferes with keratin filament formation at epidermis.

Skin cells become easily ruptured and blisters result

Plectin

Makes intermediate filaments stable and strong

Plectin mutations

• muscular dystrophy (muscle weakness)

• neurodegeneration (death of neurons)

What is nuclear envelope supported by

meshwork of intermediate filaments (nuclear lamins)

nulcear lamina functions

• structural support to nuclear envelope

• attachment site for chromosomes

nuclear lamina phosphorylation and dephosphorylation significance

When phosphorylated nuclear lamina dissemble during mitosis

When dephosphorylated nuclear lamina come back together during telophase

What do defects in nuclear lamina cause

Progeria - impaired cell division and increased cell death

specialized functions of microtubules

• build mitotic spindle for cell div.

• Bundled to form cilia

Where do microtubules grow out of

• centrosomes

• basal bodies

What are tubulin subunits made of

aB heterodimer

Protofilament structure

single strand of aB subunits stacked head to tail

• plus end with B

• minus end with a

microtubule structure

tubulin dimers pack together with the same orientation in all 13 protofilaments to give definite polarity to microtubule

centrosome structure

• spherical matrix

• pair of centrioles oriented at right angle made of short microtubules

• Y-tubulin ring

How do microtubules grow

• a minus end is embedded in centrosome

• microtubule grows out of Y-tubulin ring complexes from plus end

• B plus end extends into cytoplasm

Instability of growing microtubules

There is a rapid between some microtubules growing out of centrosome while others simultaneously shrink

What contributes to microtubule instability

B-dimer GTPase activity

Growing microtubule process

• polymerization is faster than GTPase activity of B-dimer

• GTP-cap is formed at plus end

Shrinking microtubule process

• Polymerization of microtubule is slow

• GTPase activity of B-dimer is faster than polymerization

• B-dimers are associated to GDP which has weak association

• GDP bound B-dimers are released to cytoplasm as microtubule shrinks

GTP vs GDP binding

GTP associated dimers bind much more strongly to neighbors

Drugs that affect microtubules

What stabilizes microtubules

Microtubule capping proteins on cell cortex

Do microtubules organize cell interior

Yes

Orientation of microtubule in axon and importance

All are the same with plus end facing the axon terminal

This allows for outward transport of materials in nerve cell body and inward transport of materials at nerve terminals

How do motor proteins move along microtubules

Through motor proteins globular heads

motor protein structure

• globular head at one end that interact with microtubule

• tail at one end that interacts with cargo

Two major motor proteins direction across microtubule

• dynein (moves toward minus end)

• kinesin (moves toward plus end)

Process of motor proteins moving across microtubule

• leading globular head is associated to ADP and lagging head is associated to ATP

• hydrolysis of ATP releases attachment of lagging head to microtubule

• The release of ADP and binding of ATP causes conformational change to leading head

• conformational change allows for ADP associated lagging head to be moved ahead of ATP associated leading strand

• original orientation is retained

ADP positioning difference for dynein vs kinesin

dynein: ADP is closer to minus end than ATP

kinesin: ADP is closer to plus end than ATP

Different types of kinesin transport

Can either:

• directly bind cargo to tail

• bind cargo to adaptor protein associated to tail

Dynein transport

Always uses adaptor proteins to bind cargo and deliver to minus end

Importance of microtubules and motor proteins with organelles

They determine position of organelles in cytoplasm

Microtubules in cilium or flagellum structure

• 2 central microtubules

• 9 outer doublet microtubules

• Two rows of dynein arms on outer microtubule surface that contact adjacent microtubule to generate beating force

• nexin that link 9 microtubule doublets together

• radial spoke

Cilia movement

• Power stroke: fully extended cilium quickly moves fluid over cells surface

• recovery stroke: cilium curls back into position and minimally interacts with outside fluid

Cilium cycles between these two phases

Kartangers syndrome

mutation in ciliary dynein