1. Governs cell form and polarity

2. Mediates cell movement and cell locomotion

3. Mediates organelle movement and vesicular transport

4. Cell machinery for cell division

Dynamic polymers: frequently undergo assembly/disassembly rxns

Critical to functionality of structural filaments and motors

1. Intermediate filaments: numerous subunits, form long fibrous filaments (8-12 nm)

2. Microtubules (tubulin and associated proteins): Tubulins alpha/beta/gamma subunits, form long cylindrical tubes (25 nm)

3. Microfilaments (actin and associated proteins): Actins alpha/beta/gamma subunits, form long thin filaments and meshworks (6-8 nm)

1. N-terminal globular head domain. Varies in size between different IFs

2. 40 nm rod-like domain. Coiled coil dimer between 2 alpha-helices

3. C-terminal global tail domain 

1. 2 subunits form parallel dimer

2. 2 dimers form anti-parallel tetramer

3. Tetramers form protofilaments. Intertwine in helical pattern within polymer

1. Greater thermal stability, meaning lower breakage problems

2. Can bend easily but not be pulled apart

1. Subunits: vary from 50-200 kD

2. Classified by ability to copolymerize

Type I/II (epithelial). Keratins (cytokeratins)

Type III Vimentin-like: Vimentin and 3 related proteins

Type IV: Axonal/Neurofilaments

Type V: Nuclear/Nuclear lamins

1. Composed of many different subunits. 44-70 kD. Found in epithelial cells

2. Acidic keratins (type I). ~15 subunits. Small C-terminal globular domains

3. Neural/basic keratins (type II). ~15 subunits. Large C-terminus globular domains

4. All keratin filaments contain equimolar parts acidic and basic/neutral subunits

5. Hard cytokeratins present in wool/hair/horns. Extensive disulfide bonding

For epidermolysis bullosa:

1. Severe blistering after mild pressure

2. Mutations in keratin genes expressed in basal cell layer

3. Keratins important for resisting mechanical stresses on epidermis

1. Vimentin. From mesodermal origin. 54 kD. Found in fibroblasts, endothelia, adipocytes, white cells.

2. Desmin. In muscle. 53 kD. Found in smooth and skeletal muscle.

3. Glial fibrillary acidic protein (GFAP). 50 kD. Found in glial cells, astrolytes, Swann cells.

4. Peripherin. Nerve cells. 66 kD. Found in neurons.

1. Found in neurons

2. Present in all eukaryotes

3. Stabilize nuclear envelope and help organize chromatin

4. Contains Lamin A,B,C

1. NF-L (70 kD)

2. NF-M (150 kD)

3. NF-H (210 kD)

1. Contain nuclear localization sequence

2. Assemble into sheets on the inner nuclear membrane

3. Specific phosphorylation of lamin B involved in regulating nuclear lamina disassembly at nuclear envelope breakdown (NEB) and re-assembly during mitosis

1. Vimentin desmin

2. Muscle mesoderm

3. Unknown

1. Keratin

2. Epidermis

3. IF bundling

1. Vimentin desmin

2. Muscle

3. IF crosslinking

1. Vimentin

2. Mesoderm

3. IF crosslinking

1. Vimentin desmin

2. Mesoderm muscle

3. IF crosslinking

1. Lamins A, B, & C

2. Nuclear lamina (inner lining of nuclear envelope)

1. Vimentin, desmin, glial fibrillary acidic protein, peripherin

2. Muscle, glial cells, some neurons

1. Type 1 keratins (acidic), type 2 keratins (basic)

2. Epithelial cells and their derivatives

1. Neurofilament proteins (NF-L, -M, -H)

2. Neurons

1. AKA Amyotrophic lateral sclerosis

2. Mutation in neurofilaments

3. NF-L or -H key in causing disease

4. No signals shooting across axons

5. Is what Stephen Hawking has

1. Stabilize nucleus

2. Organize cell during split

3. Forms mesh covering for protection

1. In all eukaryotic cells

2. For cell architecture and vesicle trafficking

3. Maintain cell shape and polarity

4. Determine the distribution of other cytoskeletal filaments

5. Position the organelles

6. Provide "tracks" for vesicles and chromosomes

How are microtubulues linked to MTOCs for the following:

1. Ciliates/ flagellates

2. Interphase

3. Neurons

4. Mitosis

1. Basal bodies

2. Centrosomes

3. Centrosomes

4. Spindle poles

1. Alpha, beta, and sometimes gamma subunits.

2. Gamma subunit specific example - MTOC centrosome/ spindle poles.

3. Multiple isotypes of each subunit exist and are coded by separate genes (6 alpha and 6 beta)

1. Nucleation: formation and dimers, association of dimers into protofilaments, lateral association of protofilaments to form tubulin wall

2. Elongation and propogation of microtubule from dimers

1. Nucleation

2. Elongation

3. Steady-state/ equilibrium

1. Growth: rate of tubulin assembly  > rate of GTP hydrolysis. Subunits have higher affinity for one another, making tubulin cap stable and growth stable.

2. Shrinking: GTP hydrolyze faster than assembly and expose beta end. Terms a catastrophe. Causes rapid shrinkage.

3. When cap reforms, tubulin able to grow again. Termed a rescue.

1. Colchicine: Monomer sequestering. Stops nucleation of tubulin

2. Taxol: Polymer stabilizing. Keeps microtubules at SS

1. Centrosome is an MTOC

2. Contains lots of alpha tubulin and alpha tubulin ring complex

3. Contains a pair of orthogonal centrioles

4. Centrioles organize centrosome matrix and ensure duplication during cell division 

1. Bind at side of MT and stabilize against disassembly

2. Mediate the interactions of other MTs

3. Targets of various kinases

1. Both: shift rxn kinetics in favor of adding new subunits; stabilize SS microtubule, like taxol

2. Tau - possibly from overexpression of tau in brain, leading to Alzheimer's from aggregated proteins