Ctb 5: If/ Actin Filaments

Front 1

list several types of intermediate filaments found in cells

Back 1

nuclear lains, vimentin, desmin, glial fibrillary acdic protein, keratin, neurofilaments

Front 2

What is the cause of emery-dreifuss muscular dystrophy

Back 2

autosomal dominant mutation of gene enconding lamins A/C (intermediate filaments), leads to peripheral heterocrhomatin detached from inner nuclear membrane, progressive muscle weakness, joint contractures, and cardiomyopathy

Front 3

How can intermediate filaments be used to type tumors

Back 3

Each type of tissue expresses diferenent types of IF's. Breast and GI primary cancers are keratin positive, sarcomas are vmentin positive

Front 4

What is the role of keratin intermediate filaments in epidermolysis bullosa simplex

Back 4

genetically defective keratin filaments in skin epithelial cells renders the cells suceptible to mechanical rupturing producing blistering of the skin

Front 5

Describe the protein structure of intermediate filament proteins

Back 5

Firbous molecules with conserved alpha-helical rod domains that provide for charge bonding of subunits into dimers and tetramers. They have variable carboxyl and amino terminal sequences which give functional diversity (keratin vs. lamins etc)

Front 6

Describe the polymerized structure of intermediate filaments

Back 6

The monomers assemble into dimers and then form staggered antiparallel tertramers packing to form a non-polarized, high-tensile strength insoluble filament.

Front 7

What mediates assembly/ disassebmley of intermediate filaments

Back 7

subunits phosphorylation (assembly) and dephosphorylation (disassembly)

Front 8

Describe how actin filaments (F actin) form

Back 8

Globular (G) actin binds ATP and polymerizes into F actin filaments. Note that ATP hydrolysis and polymerization are not tightly coupled and an ATP cap favors stability of F actin

Front 9

Describe actin treadmilling

Back 9

IF both ends of F actin are ezxposed, polymerization will proceed until the concentration of free monomers exceeds Cc for the plus end but below for the minus end. At this state, there will be assembly at the plus end and disassembly at the minus end but the filament will maintain a constant length even though there is a net flux of subunits through the polymer.

Front 10

Which state of actin (polymerized or free) is favored in the cell? how does the cell control the favored state

Back 10

Polymerization is highly favored because the free actin pool is greater than teh crtical concentration. To control polymerization, the cell uses binding proteins.

Front 11

What affect do mushroom toxins like cytochalasin and phalloidin have on actin filaments

Back 11

Phalloidins stabilize F actin by locking subunits together. Cytochalasins depolymize F actin by binding to the plus end.

Front 12

List 4 classes of actin binding proteins

Back 12

1. regulatory 2. severing 3. cross-linking 4. motor (myosin)

Front 13

Describe the role of actin cross linking proteins. How do they work

Back 13

Cross linking proteins give actin additional structure. The proteins have two actin binding sites sepaated by divergent intervening sequences. The proteins generate parallel and orthogonal actin arrays. Note that binding to the actin is inhibited by Ca. Examples include stress fivers which permit intercalation of mysion thick filamnets for contraction of connective tissues and formation of the cores of microvilli, orthagonal cross-linking produces an actin gel which dissovles into a sol and regulates cytoplasmic fluidity

Front 14

Describe the role of F actin in duchenne muscular dystrophy

Back 14

Mutations alter or eliminate dyrophin binding to cortical F actin resulting in repeated cell membrane ruptures and muscle cell degernation.

Front 15

Describe the role of actin in amoeboid movement

Back 15

The protruding edge of a crawling cell extends through dynamic assembly/ disassembly of actin filaments in a branching network.

Front 16

Describe th erole of actin filaments in macrphage phagocytosis

Back 16

Dependent on actin based lamellipodia formation. Note that defecgtive phagocytosis occurs in Wiskott-Aldrich syndrome