BIOL 4100 EX3

Cytoskeleton

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

Cytoskeleton

responsible for spatial organization of the cell including dividing chromosomes in metaphase/anaphase, and organelle trafficking

Cytoskeleton

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

Cytoskeleton

Generates coordinated forces that enable the cell to move and/or change shape. (i.e. cell migration, chemotaxis)

cytoskeleton

A highly dynamic structure

microfilaments (actin), Microtubules (tubulin), and Intermediate Filaments

The three main types of cytoskeletal polymers are:

Microfilaments

Highly organized NETWORKS of polar polymers and actin binding proteins that respond to local signaling activity (Myosin protein motors)

Microtubules

Long polar TUBES interacting with microtubule-associating proteins, dynamically instable (dynein and kinesin protein motors)

Intermediate filaments

Family of related non-polar proteins that function mainly in strengthening of the cytoskeleton, respond to mechanical stress on the cell, (cannot support mol. motors)

cortex

the crosslinked, contractile networks of actin microfilaments

Stress fibers

antiparallel contractile structures of actin microfilaments

lamellipodia

branched and crosslinked networks of actin microfilaments

filopodia

parallel and crosslinked bundles of actin microfilaments

this cytoskeletal polymer is highly conserved, has ATPase activity (straightening with ATP), and acts spontaneously

critical concentration

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

barbed end

positive end of an actin microfilament polymer, actin monomers are added faster

pointed end

negative end of an actin microfilament polymer, actin monomers are added slower / removed in treadmilling

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

actin microfilaments

formed from G-actin monomers in a spontaneous but controlled mechanism with different models of nucleation events

Tip-Nucleation Model

in this nucleation model, formin dimers bind to profilin on a g-actin monomer, after the monomer is released it is added to growing end of the filament

Formin

with APC-C dimer, binds to profilin on a g-actin monomer, adds monomers to growing filament

Profilin

bound to g-actin monomers, formin binds here to attach monomers this releases.

Arp2/3 Mediated Model

in this nucleation model, Arp2/3 Complex binds to sides OR pointed (-) end of filaments, where nucleation promotion factors deliver G-actin subunits to the anchored complex, and they are added to the barbed (+) end of the growing filament

Arp2/3 complex

anchors itself to the pointed (-) end of actin filaments, adds G-actin subunits to the barbed (+) end of the growing filament

NUCLEATION PROMOTION FACTORS

delivers g-actin subunits to the anchored Arp2/3 COMPLEX

lamellipodia

These are branched networks in actin polymers associated with Cell Movement and Shape Changes, and they can generate force when assembled at cell surface. (Arp2/3 Complex, NPFs)

Primer

short actin filament that recruits Arp2/3 to existing microfilament

Capping Proteins

bind to the end of actin filaments to prevent further extension

filopodia

this parallel structure of actin polymers produces longer filaments than can change alignment and produce other architectures, but produces limited force

fascin

a filopodium from a cell with reduced expression of this will buckle and fail

Crosslinking proteins

connect 2 filaments perpendicularly, trusslike, includes alpha-Actinin, Fimbrin, Fascin

anti-capping proteins

inhibit the capping of actin microfilaments, includes Ena/VASP

Ca+2

blocks polymerization of actin filaments

Mg+2

promotes polymerization of actin filaments

crosslinkers

regulated by calcium and magnesium ions, needed for structural stability of actin filaments

stress fibers

Anti-Parallel Actin Bundles that work with crosslinkers as myosin motors, form the active part of the contractile unit

cortex

Crosslinked Networks of Actin filaments connected by crosslinker proteins, to form networks; NOT nucleated by Arp2/3

crosslinkers

these play no role in nucleation or assembly of crosslinked actin cortexes

quality

what is identified by the distance between linked filaments

CLANs

cross-linked actin networks

CLANs

adjust to outside stress applied to the cell resulting in increased elasticity

ADF/Cofilin

in high concentrations, induces disassembly of actin filaments, leading to rapid binding and severing/debranching of the filament.

ADF/Cofilin

in low concentrations of this, a filament is persistently severing and recycling itself.

Myosin Induced Disassembly

this occurs when directed motion of myosin induces filament buckling and eventually breakage when one end of the myofilament moves faster than the other one

Lamellipodia

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

Lamellipodia

this branched structure of actin filaments is nucleated by arp2/3 complex/NPFs, and has primers and capping proteins, and uses the ADF/cofilin disassembly model (Fascin, Fimbrin, alpha-Actinin)

Filopodia

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

Filopodia

this parallel structure of actin filaments is nucleated by formins/ Arp2/3 Complex, has ena/vasp proteins, and uses the ADF/cofilin disassembly model (Fascin, Fimbrin, alpha-Actinin)

Stress Fibers/Transverse Arcs

this antiparallel structure of actin filaments is nucleated by formins/ Arp2/3 Complex, has ena/vasp proteins, and uses the ADF/cofilin AND myosin disassembly model (alpha-actinin, etc., myosin)

Stress Fibers/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

Cell Cortex

this overlapping, unbranched structure of actin filaments is nucleated by ????? (NOT ARP) has ERM proteins, and uses the ADF/cofilin AND myosin disassembly model (Fimbrin, Filamin)

Invadopodia

Tiny footlike protrusions that enable highly metastatic cancer cells to invade neighboring tissues.

tubulin

alpha(-)/beta(+) dimer that makes up microtubules

hydrophobic

INTRA-ProtoTubule contact interactions are:

hydrophilic

INTER-ProtoTubule contact interactions are:

Dynamic Instability

Co-existence of growing and shrinking microtubules in the same conditions.

rescue

The transition from shrinkage to growth of a tubule

catastrophe

The transition from growth to shrinkage of a tubule

rescue

associated with the presence of GTP islands along the proto tubule

catastrophe

associated with Aging Behavior and MT- Lattice Defects

Microtubule severing enzymes

these enzymes facilitate the disassembly of microtubules, includes katanin, spastin, and fidgetin

Microtubule Organizing Center (MTOC)

Structure in eukaryotic cells from which the microtubule array emerges

Basal Bodies

microtubule array of cilia and flagella

Centrioles

microtubule array of mitotic and meiotic cells

centriole

dimerizes to form a centrosome

positive

the ____ ends of microtubules dynamically search for and capture specific sites, such as mitotic kinetochores and cell cortex

Microtubule Associating Proteins

Proteins that interact with the microtubules of the cellular cytoskeleton

Class 1

class of Microtubule Associating Proteins that promote the assembly of microtubules (two types, MAP1 and MAP2/TAU

Class 2

class of Microtubule Associating Proteins that “destabilize” microtubules (? Sometimes, includes MCAK, EB1, and Kinesin 8)

tau proteins

Hyperphosphorylation of __________ leads to dissociation from microtubule, destabilization of the microtubule and development of paired-helical filaments.

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

Dynein Walking

occurs when dynein moves along microtubules using ATP energy, grabbing and releasing the outer tubule to move

Cross-linked proteins

these cause bending in tubule doublets as the dynein exerts force on it while it moves along

Microtubules

composed of dimers of - and -tubulin polymerized into a hollow structure extending from the MTOC outward into the cytoplasm.

Microtubule associating proteins

interact along the length of the microtubule or at its ends. Depending on the interaction, stabilization, rescue or catastrophe may occur at the interaction site

Cilia and flagella

these both 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, associated with the cell’s mechanical integrity

Intermediate Filaments

this non-polar cytoskeletal polymer is elastic and strong, stable and flexible, without motor proteins, tissue specific, and not conserved across eukaryotes

Keratins

These are either acidic (I) or basic (II) and comprise classes I & II of intermediate filaments, associated with mechanical strength found in epithelial cells

Vimentin

intermediate filament associated with colon cancer

Neurofilament

intermediate filament associated with ALS

coiled-coil dimer

Basic structure of intermediate filaments with intertwined central domains

Intermediate filaments

thought to play a tension-bearing role in the cell.

Intermediate filaments

these are dynamically transported and remodeled in neurons

Intermediate Filaments

these are less susceptible to chemical attack than are MTs and microfilaments.

Keratin

Protein that protects the epithelial cells from damage and stress

acidic

Class I (alpha) keratins are :

basic

Class II (beta) keratins are :

Class III Intermediate Filaments

Intricate network of IF structures extending from the cell membrane to the nucleus that regulates cell shape, motility and organelle positioning. Includes: Desmin (muscle cells) GFAP (glial cells) Peripherin (peripheral nerves) Vimentin (fibroblasts)

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. overexpressed in cancers, most widespread IF, A/B/C

Microtubules

resist bending when a cell is compressed

Microfilaments

serve as contractile elements that generate tension

Intermediate filaments

these are elastic and can withstand tensile mechanical forces

Spectraplakins (plectin)

linker proteins that integrate MT, MF and IFs

fibrous

In contrast to microfilaments and microtubules which are both globular in basic structure, IF dimers are _________

Intermediate Filaments

the only nonpolar component of the cytoskeleton and are not associated with any known motor proteins. They are defined by a very specific structures beginning at coiled-coil dimers

Desmin GFAP Peripherin Vimentin

Match the Class III IFs to their location: muscle cells, glial cells, peripheral nerves, and fibroblasts