Cytoskeleton I Flashcards by Joel Glotfelty

Establishes cellular polarity

Cytoskeleton

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Performs directional migration

Cytoskeleton

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Responsible for the formation of the bipolar mitotic/meiotic spindle

Cytoskeleton

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What are four major roles of the cytoskeleton?

) Establishes cell polarity
) Directional migration
) formation of mitotic/meiotic spindle
) Chromosome segregation

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Also responsible for cytokinesis, intracellular transport, exocytosis, and endocytosis

Cytoskeleton

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What are the three cytoskeletal components?

-have different distributions in the cell

Actin, Intermediate filaments, Microtubules

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Cytoskeletal components have different distributions, this is important for cell

Shape & polarity, and tissue formation

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Side that is towards the lumen

Apical face

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Side that is towards the basement membrane

Basal face

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Are assembled from smaller protein subunits

Non-covalent polymers
Dynamic

Cytoskeletal structures

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Intermediate in size between actin filaments and microtubules

-more stable-the “tendons” of the cell

Intermediate filaments

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Major components of the cytoskeleton and nuclear boundary and functional organization of cellular architecture

Intermediate filaments

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Intermediate filaments provide protection from

Mechanical stress

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Viscoelastic filaments within cells and at junctions between cells

-Stress absorbers

Intermediate filaments

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Intermediate filaments have a role in signaling and controlling gene regulatory

Networks

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Do intermediate filaments have any known associated motors?

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Surround the nucleus, extend to cell periphery, and at cell-cell and cell-ECM junctions

Intermediate filaments

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Intermediate filaments are dynamic. They are controlled by

Phosphorylation

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What are four main functions of intermediate filaments?

) Mechanical support
) Cytoarchitecture
) Cell migration and movement
) Signal modulation

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Large family of proteins (~70 genes) including keratins, neurofilaments, nuclear lamins among others. Many disease-assoc. mutations.

Intermediate filaments

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What is the basic structure of an intermediate filament?

Two chained coil that assembles to form tetramer

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The N-terminal and C-terminal ends of intermediate filaments are globular, and their coiled coil region is interupted by

Linker domains

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Intermediate filaments assemble as antiparallel tetramers. In contrast to actin filaments and microtubules, the overall structure is

Not polar

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Mutations in lamins cause

Laminopathies

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Mutations in keratins cause

Skin blistering diseases

Actin filaments (F-actin) are polymers of the globular protein, actin (G-actin), that contains a bound

Nucleotide (ATP or ADP)

Are actin filaments polar?

Yes

In an actin filament, what is the 1. ) fast growing end? 2. ) slow growing end?

1. ) "plus" or barbed end | 2. ) "minus" or pointed end

The overall shape of the actin filament is

Helical

Modify the actin filament dynamics and higher order assemblies

Actin binding proteins

Both assembled from globular proteins by a condensation-polymerization mechanism to form a polar structure

Microtubules and actin filaments

The preferred end of monomer addition to actin and microtubules is the

Plus end

What do microtubules and actin filaments have at the growing end?

ATP or GTP cap

Is energy required for polymerization of actin filaments or microtubules?

Given all their similarities, are actin filaments and microtubules related?

The rate limiting step of elongating the barbed or "plus end of actin filaments or microtubules is

Nucleation

Preferentially added to the barbed (+) end of actin filaments

ATP-actin

ATP hydrolysis is not required for polymerization, but the bound nucleotide influences stability of the ends and interactions with other

Proteins

Most of an actin filament is made up of ADP-actin, with the exception of the extreme

Barbed end

In actin filaments and microtubules, hydrolysis of NTP to NDP takes place after

Polymerization

Soluble actin or microtuble subunits are in the

T form

Actin filament and microtubule polymers are a mixture of -(-) end grows so slow that hydrolysis catches up

T (NTP) and D (NDP) form

Affect microtubule growth and stability

Nucleotide at (+) end

Stabilizes the (+) growing end of the microtubule

GTP-tubulin cap

Destabilizes the microtubule resulting in rapid depolymerization

GDP-tubulin subunits at (+) end

Lengthen or shorten as a function of time -Catastrophe happens before rapid shortening

Individual microtubules

Determine the state of actin and its dynamics

Actin binding proteins

Actin binding proteins are targets of

Cell signaling cascades

A monomer or filamentous poymer -a building block

Actin

Exist as singular units or are assembled into different structures by actin binding proteins

Filaments

Actin filaments are dynamic and are ultimate targets in

Cell signaling pathways

Important in vesicular and organelle transport

Tubulin and microtubules

Form the mitotic spindle, cilia and flagella, centriole, and basal bodies

Microtubules

Many cilia are motile, but most cells have a non-motile -usually one per cell

Primary Cilium

Central in developmental signaling pathways -sensory organelles

Primary Cilium

The only difference between the structure of motile cilia and the primary cilia is the primary cilum has no

Microtubule in the center

The microtubule organizing center -forms poles of mitotic spindle

Centrosome

A consequence of the centrosome is that the (+) end of microtubules is located towards the

Cell periphery

The centrosome is organized around a pair of

Centrioles

Centrioles are surrounded by

Pericentriolar material

Centrioles duplicate beginning in

S phase of mitosis

Regulate state of microtubule assembly and stabilize or destabilize plus or minus end

Microtubule associated proteins (MAPs)

Bind to the side of microtubules and stabilize by side binding or bundle formation

MAPs

Can also sever microtubules

MAPs

An example of a MAP that acts in Alzheimer's disease in neurofibrillary tangles -connets microtubules

Tau

In order for the (+) end to reach the cell periphery, (+) tip proteins must inhibit

Catastrophes

Bind to and track with the + end of a | growing microtubule

(+) tip proteins

(+) end reaching the cell periphery allows for communication and connection with the cell cortex and interaction with the

Actin cytoskeleton

Capture chromosomes during mitosis -Associated with kinetochore

(+) end

Can alter microtubule or actin polymerization

Natural toxins

Binds and stabilizes actin filaments -found in death angel mushroom

Phalloidin

Depolimerizes microtubules -From the autumn cross

Colchicine

Binds and stabilizes microtubules - from pacific yew tree - widely used as anti-cancer drug

Taxol

Widespread: seen during development, in chemotaxis, in tissue formation and repair, and in cancer metastasis

Cell migration

Migration of neutrophils to infection sites

Chemotaxis

What are the two ways to drive cellular movement?

1. ) motor driven | 2. ) polymerization driven

Can also be motor driven or polymerization driven

Intracellular transport

Can usurp the cellular machinery

Pathogens

An example of cellular motility is when a neutrophil chases a

Bacterium

Found in the blood and protect the body from bacteria that enter through the skin

Neutrophils

Neutrophils cahse bacteria by

Chemotaxis

Mechanisms that involve actin polymerization at the leading edge and myosin dependent contractions of the tail

Chemotaxis

Can drive cell migration by itself

Actin polymerization

Can commandeer the cell's actin polymerization machinery during infection

Certain bacteria

How does actin polymerization alone provide the force for movement?

Elongation at the (+) end pushes against the membrane

More actin filaments are nucleated, existing filaments are severed to create more barbed ends, and branches are formed in existing filaments to generate the

Actin polymerization required for movement

Nucleates filaments from the sides of actin filaments, making complex branched structures -a complex of 7 proteins

Arp2/3

What activates Arp2/3 to enable it to nucleate actin filaments?

Rho-dependent signaling cascade

Dendritic (branched) actin filaments drive

Membrane protrusion

Involved in neutrophil migration, wound healing, invasion of metastatic cancer cells, and clathrin-dependent endocytosis

Arp2/3-dependent polymerization

Food born bacterium that infects intestinal epithelium and activates Arp2/3, which propels bacterium through cytoplasm

Listeria

Contain ƴ-tubulin ring complex that nucleates the 13 | protofilaments of microtubules and caps the - ends

Centrioles

WASP/Scar binds to Arp2/3 complex and activates it. The complex then binds to existing filaments and makes a -generates actin-polymerized movement

New filament growing out (branch)