32. Cytoskeleton
The cytoskeleton is important in determining the cell shape, protect against mechanical stress, move organelles around and many other things. Three types of filaments comprise the cytoskeleton, microtubules, intermediate filaments and microfilaments. A protein called plectin binds all three types together to form the necessary 3d structure.
Microtubules
Microtubules in the neurons and CNS are stabilized by a protein called tau. Tau can be phosphorylated at many points on the protein. When tau is phosphorylated on many points, the microtubule it is attached to is disassembled. In this way can the assembly and disassembly be regulated by kinases and phosphorylases that either phosphorylate or dephosphorylate the tau protein, respectively.
Excess phosphorylation of tau is associated with many diseases, collectively called taupathies. When tau is hyperphosphorylated will not only the microtubules be degraded, but the tau proteins themselves will form clumps called neurofibrillary tangles. These clumps are markers for all taupathies. Alzheimer’s, Parkinson’s and Pick’s diseases are all examples of taupathies.
The microtubule network in the cell works as highways for certain proteins to travel on. These motor proteins are called kinesins and dyneins. Kinesins travel toward the periphery of the cell while dyneins travel toward the center of the cell.
Intermediate filaments
Many types of intermediate filaments exist. Intermediate filaments are very tissue-specific, meaning that different tissues and cell types express different types of these filaments. They’re summarized in the table below.
| Type | Building blocks | Found where? |
|---|---|---|
| Nuclear | Lamin A, B and C | In the nuclear envelope |
| Vimentin-like | Vimentin | In every cell at the beginning of differentiation |
| Vimentin-like | GFAP | In glial cells |
| Vimentin-like | Periferin | In neurons |
| Epithelial | Keratin type I and type II | In epithelial cells |
| Axonal | Neurofilaments | In neurons |
| Desmin | Desmin | Myocytes |
The fact that different tissues express different types of intermediate filaments is very important medically in cancer metastasis. By finding out which type of intermediate filaments the cancer cells contain, it can be determined what type of tissue the cancer originated in.
Like microtubules, the disassembly and assembly of intermediate filaments is also regulated by phosphorylation. In almost all cases, phosphorylation of the intermediate filaments causes them to be disassembled. The kinases that can phosphorylate intermediate filaments are PKA, PKC and MAPK.
Many diseases are associated with the dysfunction of lamin type A and type C, like Charcot-Marie-Tooth syndrome.
Microfilaments (actin)
Microfilaments are comprised of a protein called F-actin, or just actin. A protein called the Arp2/3 complex controls the branching of actin. Formin initiates the polymerization of actin.
The Arp2/3 complex is activated by three proteins, WASP, WAVE and cortactin. EGF activates a protein called Rac which activates WAVE and cortacin to induce remodeling of the cytoskeleton.