Literature: A-K ; L-Z ; subject area
Compiled by: Julian Thorpe
Cytoskeleton
|
Please Note: Due to time constraints, the text part of this page has not been updated for some time. However, references are added reasonably frequently. |
The disruption of
the cytoskeleton is a key feature of AD, so
here is some general background:
The cytoskeleton is a complex mixture of proteins
which together act to maintain cell shape and facilitate the
movement of particles and organelles within the cytoplasm. The
overall cytoskeletal structure is very dynamic as the component
proteins may go through rapid cycles of polymerisation and disassembly.
These proteins may be broadly grouped into 3 types:
5-7nm thick filaments of F-actin which function as contractile elements when associated with the complementary contractile protein myosin (to form actinomyosin ). May also be laterally associated with other proteins and sometimes anchored to membranes.
2. Intermediate filaments:
N.B. See Intermediate
filaments of neural/glial cells
for more detail on intermediate filaments specific
to neurons and glial cells, research results, etc.
 | So named because of their intermediate size (c. 10nm) between the microfilaments and microtubules. |
| Contain a characteristic central alpha-helical domain that forms coiled-coil rods. The latter can assemble into filaments. |
| Responsible for cell shape maintenance and conferring some strength and rigidity. |
| The protein subunits of intermediate filaments show considerable diversity and tissue specificity. |
Types:
| Type I and II:keratins of epithelial cells. |
| Type III: vimentin (mesenchymal cells); desmin (muscle); glial fibrillary acidic protein (astroglia); peripherin (peripheral neurons) |
| Type IV: neurofilaments of neuronal cell types |
| Type V: nuclear lammins. |
| They are c. 25nm in width and composed of tubulin . |
| Involved in the maintenance of cell shape and in the movement of organelles, cell products and chromosomes during cell division. They are also the components of cilia and flagella. |
| Play a crucial role in neuronal development as neuritic outgrowth is dependent upon microtubule assembly ( Yamada et al., 1970 ). |
| Microtubules and their associated proteins also form the basis of axonal transport. |
| The microtubules are associated with other proteins such as dynein and kinesin and also the MAPs ( microtubule-associated proteins ). Of the latter MAP1A and 1B (c. 350kD) and MAP2A and 2B (270kD) form projections from microtubules within brain cells. MAP2 is a distinguishing protein within axonal processes of neurones. |
| The MAP tau is as an elongated molecule (about 35-50 nm long, dependent on the isoform) without recognizable secondary structure ( Mandelkow et al., 1995). Its role may be likened to that of 'ties' which hold the microtubular tracks in place. There is a mixture of up to 6 isoforms in the human brain which are generated from a single gene by alternative splicing. Range in size from 352-441 amino acids ( Goedert et al., 1989). The recent finding that mutations in the tau gene are responsible for frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) has provided convincing evidence that tau protein plays a key role in neurodegeneration ( Hutton et al., 1998 ) and suggests that distinct sets of tau isoforms expressed in different neuronal populations could lead to different pathologies (see review: Buee et al., 2000 ). It appears to be enriched in axons, probably playing a role in axonal development, and it is the inappropriate hyperphosphorylation of this protein in AD which contributes towards neurofibrillary tangle development. |
N.B. Please visit the website of the 'Institut National de la Sante et de la Recherche Medical' for detail on tau protein in relation to neurodegeneration
(These journals include: Neurology, Neurobiology of Disease, Journal of Neurochemistry, Alzheimer's Disease Review)
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