MAP2/TAU family
Tau is a vertebrate microtubule-associated protein (MAP) of the MAP2/Tau family. MAP2/Tau family includes not only Tau but also other MAPs, like MAP2 and MAP4 in vertebrates, and their respective homologues in other animals. MAP2 and Tau are found in neurons, whereas MAP4 is generally found in other tissues but is absent in neurons. All isoforms of MAPs share a conserved C-terminal domain containing tubulin-binding repeats and a N-terminal projection domain of varying length [1]. The N-terminus of Tau has a net negative charge, resulting a long-range (>100 nm) repulsive force. This force is highly entropic, providing a physical mechanism for maintaining microtubule spacing, which then might facilitates efficient organelle transport [2]. Other than the microtubule-based movements, new MAP functions are being continuously discovered.
TAU
Protein description:
Homo sapiens: 758(PNS) AA; sequence complete with definitive experimental evidence at protein level established.
Mus Musculus: 733 Amino Acids; sequence complete with definitive experimental evidence at protein level established.
Macaca mulatta: 459 Amino Acids; sequence complete with definitive experimental evidence at protein level established
Functions:
Microtubule-associated protein Tau is encoded by MAPT gene and is located within various regions including cell membrane, peripheral membrane protein, cytoskeleton, and axon.
Tau shows identical functions in all 3 species- it regulates microtubule dynamics and promotes microtubule assembly and stability. The biological roles of Tau, therefore, include positive regulation of microtubule polymerization, regulation of movement of organelles, neuron migration, and cell cycle.
Additionally, Tau also establishes and maintains neuronal polarity. Tau works as a linker protein between axonal microtubules and neural plasma components: The C- and N-termini of Tau bind to the axonal microtubules and neural plasma components repectively. Axonal polarity is predetermined by Tau localization the cell body body of neuronal cells [3].
There are 9 human isoforms found: the long isoforms allow stabilisation of cytoskeleton whereas the shorter isogorms modulate its plasticity.
Tau-F displays that the proline-rich (residues 172-251) and C-terminal tail (residues 368-441) regions of Tau are its phosphorylation sites in which the regions flank the microtubule-binding repeats.[4] Hyperphosphorylated forms of Tau have been linked to Alzheimer's disease.
MAP2
Protein description:
Homo sapiens: 1827 Amino Acids; sequence complete with definitive experimental evidence at protein level established
Mus Musculus: 1828 Amino Acids; sequence complete with definitive experimental evidence at protein level established
Macaca mulatta: 1827 Amino acids; incomplete sequence; unreviewed.
Functions:
MAP2 (microtubule-associated protein 2), is encoded by MAP2 gene at chromosome 2q34-q35 and is subcellularly located within the cytoskeleton.The exact function of MAP2 is unknown, but MAP2 was found to stabilise and stiffen the microtubules against depolymerisation.
Biological functions of MAP2 were found in human and mouse but its functions in monkey are still unclear. In humans and mice, MAP2 participates in dendrite development, microtubule bundle formation, and cellular response to organic substance mainly by change in movements [5-7]. Additionally, MAP2 functions in axonogenesis as neuronal process extension is dependent on the reorganization of microtubules. Microtubules are reorganized or transported within the neurites of developing neurons.
MAP2 is a prominent large-sized component of purified brain microtubules that, like the 36-38KDa tau proteins, bears antigenic determinants, associated with the neurofibrillary tangles in Alzheimer's disease [8].
MAP4
Protein description:
Homo sapiens: 1152 Amino Acids; sequence complete with definitive experimental evidence at protein level established
Mus musculus: 1125 Amino Acids; sequence complete with definitive experimental evidence at protein level established
Macaca mulatta: 1126 Amino acids; incomplete sequence; unreviewed.
Functions:
Unlike MAP2 and Tau, MAP4 is a non-neuronal microtubule-associated protein,only located in the cytoskeleton. MAP4 has 4 repeats, each containing a microtubule binding domain that shares homology with neural microtubule-associated proteins MAP2 and Tau [9].
Though MAP4 is non-neuronal, its 4 isoforms show similar degrees of microtubule binding affinity and microtubule assembly promoting activity [10].
Like Tau, Ser787 of human MAP4 is a critical phosphorylation site causing microtubules to be dynamic at mitosis. Mutation of Ser787 to Glu notably reduces microtubule-polymerization activity of MAP4 [11].
MAP4 regulates the surface charge of microtubules [3], enabling microtubule-based movements. It also regulates cell mitosis by establishing spindle orientation and organization.
Like MAP2, such functions of MAP4 are not identified in monkey, compared to human and mice [12-14].
References
1. http://www.ncbi.nlm.nih.gov/pubmed/15642108
3. http://www.ncbi.nlm.nih.gov/pubmed/21985311
4. http://www.ncbi.nlm.nih.gov/pubmed/18052981
5. http://www.uniprot.org/uniprot/P11137
6. http://www.uniprot.org/uniprot/P20357
7. http://www.uniprot.org/uniprot/I2CTK4
8. http://www.ncbi.nlm.nih.gov/pubmed/3142041
9. http://www.ncbi.nlm.nih.gov/pubmed/1905296
10. http://www.ncbi.nlm.nih.gov/pubmed/12773533
12. http://www.uniprot.org/uniprot/P27816
13. http://www.uniprot.org/uniprot/P27546
14. http://www.uniprot.org/uniprot/A0A059TER6
© 2015. CELL2008. Group 13: Andreas Millios, Rebecca Johnson, Dilen Ghetia, Fraz Azizi, Dominic Scaglioni, Nayoon Jang, Hannah De Bruijn.