Block2 7.cytoskeleton

Front 1

a,beta Dystroglycan

Back 1

Part of a transmembrane protein complex associated with muscular dystrophy. Dystrophin binds this from cytosolic side of plasma membrane. It associates with laminin in the extra-cellular matrix

Front 2

Laminin

Back 2

Laminin is a protein in the extracellular matrix that is binding to the a,b dystroglycan

Front 3

Dystrophin

Back 3

Dystrophin links the actin cytoskeleton of muscles to the extracellular matrix and is thought to stabilize the plasma membrane during muscle contraction.
•The absence of dystrophin leads to increased death and destruction of muscle cells.
•Scar tissue (a mix of collagen and blood vessels) begins to replace the muscle fibers.
•The contraction of fibrous scar tissue around muscle cells leads to muscle deformity and muscle dysfunction.

Front 4

Actin

Back 4

Actin microfilaments. ATP and Mg2+ are important in polymerization. Globular or filamentous. Essentially the same as tubulin dimers in the way they grow on plus ends of microfilament, bound with ATP they are more stable than ADP.

Front 5

Thymosin B4 - important

Back 5

binds to ATP-G-actin and sequesters it from the polymerization process. As the concentration of ATP-G-actin is reduced by polymerization, more is released by thymosin-β4. It is a way to control growth.

Front 6

Profilin - important

Back 6

Pro = more. Enhances exchange of ADP for ATP on G-actin, increasing rate of filament formation

Front 7

Cofilin - important

Back 7

Bind to F-actin whose subunits contain ADP. When it binds, it breaks the actin filament into shorter pieces. This generates more – ends and therefore enhances the disassembly of the filament

Front 8

CapZ

Back 8

"Caps" it and stops it. Binds at the + end of the filament and prevents the addition of new G-actin monomers. The activity of CapZ is tightly controlled by signal transduction molecules in the cell and by other regulatory proteins that bind at the + end

Front 9

Tropomodulin

Back 9

binds at the - end and stabilizes the filaments.

Front 10

Formin

Back 10

Formin = formation. Stimulates formation of long, unbranched filaments found in stress fibers and the contractile ring. Activated by Rho

Front 11

Arp2/3 Complex

Back 11

The slash looks like a branch. Stimulates formation of branched filaments found in leading edge of migrating cells. Activated by Cdc42 and Rac G-proteins, who are activated in response to growth factors binding a receptor

Front 12

4 steps of cell migration

Back 12

1.Extension of lamellipodium at the leading edge of the cell.
2.Formation of new focal adhesions.
3.Bulk of cell cytoplasm flows forward due to contractions at the rear of the cell.
4. Detachment at the rear of the cell and endocytosis/recycling of membrane proteins involved in cell adhesion

Front 13

Cdc42 and Rac

Back 13

Extension of membrane at leading edge of cells is nucleated by the Arp2/3 complex, and controlled by Cdc42 and Rac, two membrane G proteins activated by growth factors

Front 14

Rho

Back 14

Activation of Rho (another G protein) at the trailing edge of the cell activates the actin nucleating protein formin and leads to stress fiber formation. Rho activation also activates Rho kinase, which then activates myosin II and causes the back of the cell to contract. Rho activation blocks Rac activation, thus establishing polarity within the cell. Exerts its action at the back of the moving cell. Also increases myosin activity

Front 15

Fimbrin

Back 15

Actin cross-linking protein, organizes filaments in microvilli

Front 16

α-actinin

Back 16

Actin cross-linking protein, organizes filaments in stress fibers, filapodia, muscle Z-line

Front 17

Spectrin

Back 17

Yo, spectrin at the cortex (of the cell) Actin cross-linking protein, organizes filaments at the cell cortex (around edge of cell). A defect can result in small, fragile RBC's called Hereditary Sphereocytosis.

Front 18

Integrins

Back 18

Link cytoskeletal components to the extracellular matrix and generate intercellular signals that lead to formation of focal adhesions

Front 19

Hereditary Sphereocytosis

Back 19

Red blood cells small and fragile because of a defect in spectrin, protein 4.1 or ankyrin. Patients usually have anemia and enlarged spleens because of the enhanced breakdown of RBCs. Gallstones composed of bilirubin are also common because of the large quantities of heme that must be degraded

Front 20

Intermediate Filaments

Back 20

Stable, mainly structural filaments, network throughout cell. Use phosphorylation to control subunit exchange. Antibodies to intermediate filaments proteins are used for tumor typing

Front 21

Desmosomes and hemidesmosomes

Back 21

IF's found here, cell-cell contacts particularly in epithelial cells, reduces friction

Front 22

epidermolysis bullosa

Back 22

Mutations in IF's: keratins 5 or 14

Front 23

amylotrophic lateral sclerosis or Lou Gehrig disease

Back 23

Mutations in IF's: neurofilaments

Front 24

Keratins (acidic and basic)

Back 24

Intermediate filament proteins found mainly in epithelial cells, associated with desmosomes

Front 25

Desmin, Vimentin

Back 25

(Desmond Howard = fast twitch muscle) Intermediate filament proteins in muscle, glial, mesenchymal cells. Function is sarcomere organization and integrity

Front 26

Lamins

Back 26

Intermediate filament proteins in nucleus. Nuclear structure and organization