Microtubule-associated protein 2 explained
Microtubule-associated protein 2 is a protein in humans that is encoded by the MAP2 gene.[1] [2]
Function
This gene encodes a protein that belongs to the microtubule-associated protein family. The proteins of this family were originally isolated since they copurify with tubulin in polymerization experiments: tubulin in cell extracts can be made to polymerize to produce microtubules (MT) under the influence of heat and the addition of GTP, and the MT can then be collected by centrifugation. When this is done a series of microtubule associated proteins are collected along with the MT and can be detected by SDS-PAGE and other methods. Brain extracts are rich in several of these proteins, MAP2 being one of these. The single MAP2 gene produces four major transcripts producing four proteins, MAP2A, MAP2B, MAP2C and MAP2D. MAP2A and MAP2B are very high molecular weight proteins, with apparent molecular weight on SDS-PAGE about 250 kDa, while MAP2C and MAP2D are much lower molecular weight forms with apparent SDS-PAGE size about 70 kDa.[3] All forms of MAP2 share a common core sequence which includes MT binding domains, 18 amino acid sequences which are found in other MT associated proteins such as MAP Tau and MAP1B. The MAP2 isoforms are thought to be involved in MT assembly, which is an essential step in neuritogenesis. MAP2 serves to stabilize MT growth by crosslinking MT with intermediate filaments and other MTs. MAP2 isoforms are neuron-specific cytoskeletal proteins enriched in dendrites and perikarya, implicating a role in determining and stabilizing neuronal morphology during neuron development. As a result antibodies to MAP2 are widely used to identify neuronal cells and trace dendritic processes in experimental contexts.
Interactions
MAP2 has been shown to interact with Grb2,[4] [5] NEFL[6] and MYO7A.[7] All MAP2 isoforms bind to microtubules.
References
Further reading
- Roses AD, Einstein G, Gilbert J, Goedert M, Han SH, Huang D, Hulette C, Masliah E, Pericak-Vance MA, Saunders AM, Schmechel DE, Strittmatter WJ, Weisgraber KH, Xi PT . Morphological, biochemical, and genetic support for an apolipoprotein E effect on microtubular metabolism . Ann. N. Y. Acad. Sci. . 777 . 146–57 . 1996 . 1 . 8624078 . 10.1111/j.1749-6632.1996.tb34413.x . 1996NYASA.777..146R . 9145181 .
- Snásel J, Pichová I . The cleavage of host cell proteins by HIV-1 protease . Folia Biol. (Praha) . 42 . 5 . 227–30 . 1997 . 8997639 . 10.1007/BF02818986 . 7617882 .
- Shafit-Zagardo B, Kalcheva N . Making sense of the multiple MAP-2 transcripts and their role in the neuron . Mol. Neurobiol. . 16 . 2 . 149–62 . 1999 . 9588626 . 10.1007/BF02740642 . 2966442 .
- Liu Y, Saad RS, Shen SS, Silverman JF . Diagnostic value of microtubule-associated protein-2 (MAP-2) for neuroendocrine neoplasms . Advances in Anatomic Pathology . 10 . 2 . 101–6 . 2003 . 12605092 . 10.1097/00125480-200303000-00005 .
- Ainsztein AM, Purich DL . Cleavage of bovine brain microtubule-associated protein-2 by human immunodeficiency virus proteinase . J. Neurochem. . 59 . 3 . 874–80 . 1992 . 1494913 . 10.1111/j.1471-4159.1992.tb08325.x . 40571317 .
- Alberts MJ, Kandt RS, Pericak-Vance MA, Bebout J, Speer MC, Siddique TS, Yamaoka L, Hung WY, Gaskell PC, Roses AD . MspI RFLP for microtubule associated protein-2 (MAP2) . Nucleic Acids Res. . 19 . 4 . 960 . 1991 . 1708129 . 333743 . 10.1093/nar/19.4.960 .
- Wallin M, Deinum J, Goobar L, Danielson UH . Proteolytic cleavage of microtubule-associated proteins by retroviral proteinases . J. Gen. Virol. . 71 . 9 . 1985–91 . 1990 . 2212989 . 10.1099/0022-1317-71-9-1985 . free .
- Kosik KS, Orecchio LD, Bakalis S, Duffy L, Neve RL . Partial sequence of MAP2 in the region of a shared epitope with Alzheimer neurofibrillary tangles . J. Neurochem. . 51 . 2 . 587–98 . 1988 . 2455776 . 10.1111/j.1471-4159.1988.tb01079.x . 31087371 .
- Dammerman M, Yen SH, Shafit-Zagardo B . Sequence of a human MAP-2 region sharing epitopes with Alzheimer neurofibrillary tangles . J. Neurosci. Res. . 24 . 4 . 487–95 . 1990 . 2481044 . 10.1002/jnr.490240405 . 25209290 .
- Obar RA, Dingus J, Bayley H, Vallee RB . The RII subunit of cAMP-dependent protein kinase binds to a common amino-terminal domain in microtubule-associated proteins 2A, 2B, and 2C . Neuron . 3 . 5 . 639–45 . 1990 . 2561973 . 10.1016/0896-6273(89)90274-2 . 1329548 .
- Rubino HM, Dammerman M, Shafit-Zagardo B, Erlichman J . Localization and characterization of the binding site for the regulatory subunit of type II cAMP-dependent protein kinase on MAP2 . Neuron . 3 . 5 . 631–8 . 1990 . 2701845 . 10.1016/0896-6273(89)90273-0 . 45499202 .
- Herrmann H, Wiche G . Plectin and IFAP-300K are homologous proteins binding to microtubule-associated proteins 1 and 2 and to the 240-kilodalton subunit of spectrin . J. Biol. Chem. . 262 . 3 . 1320–5 . 1987 . 10.1016/S0021-9258(19)75789-5 . 3027087 . free .
- Garner CC, Tucker RP, Matus A . Selective localization of messenger RNA for cytoskeletal protein MAP2 in dendrites . Nature . 336 . 6200 . 674–7 . 1989 . 3200318 . 10.1038/336674a0 . 4368119 .
- Takahashi M, Tomizawa K, Sato K, Ohtake A, Omori A . A novel tau-tubulin kinase from bovine brain . FEBS Lett. . 372 . 1 . 59–64 . 1995 . 7556643 . 10.1016/0014-5793(95)00955-9 . 42295269 . free .
- Kindler S, Garner CC . Four repeat MAP2 isoforms in human and rat brain . Brain Res. Mol. Brain Res. . 26 . 1–2 . 218–24 . 1995 . 7854050 . 10.1016/0169-328X(94)90093-0 .
- Albala JS, Kalcheva N, Shafit-Zagardo B . Characterization of the transcripts encoding two isoforms of human microtubule-associated protein-2 (MAP-2) . Gene . 136 . 1–2 . 377–8 . 1994 . 8294038 . 10.1016/0378-1119(93)90502-T .
- Illenberger S, Drewes G, Trinczek B, Biernat J, Meyer HE, Olmsted JB, Mandelkow EM, Mandelkow E . Phosphorylation of microtubule-associated proteins MAP2 and MAP4 by the protein kinase p110mark. Phosphorylation sites and regulation of microtubule dynamics . J. Biol. Chem. . 271 . 18 . 10834–43 . 1996 . 8631898 . 10.1074/jbc.271.18.10834 . free .
- Björkblom B, Ostman N, Hongisto V, Komarovski V, Filén JJ, Nyman TA, Kallunki T, Courtney MJ, Coffey ET . Constitutively active cytoplasmic c-Jun N-terminal kinase 1 is a dominant regulator of dendritic architecture: role of microtubule-associated protein 2 as an effector . J. Neurosci. . 25 . 27 . 6350–61 . 2005 . 16000625 . 6725281 . 10.1523/JNEUROSCI.1517-05.2005 .
Notes and References
- Neve RL, Harris P, Kosik KS, Kurnit DM, Donlon TA . Identification of cDNA clones for the human microtubule-associated protein tau and chromosomal localization of the genes for tau and microtubule-associated protein 2 . Brain Res . 387 . 3 . 271–80 . May 1987 . 3103857 . 10.1016/0169-328x(86)90033-1.
- Kalcheva N, Albala J, O'Guin K, Rubino H, Garner C, Shafit-Zagardo B . Genomic structure of human microtubule-associated protein 2 (MAP-2) and characterization of additional MAP-2 isoforms . Proc Natl Acad Sci U S A . 92 . 24 . 10894–8 . December 1995 . 7479905 . 40537 . 10.1073/pnas.92.24.10894 . 1995PNAS...9210894K . free .
- Web site: Entrez Gene: MAP2 microtubule-associated protein 2.
- Lim RW, Halpain S . Regulated association of microtubule-associated protein 2 (MAP2) with Src and Grb2: evidence for MAP2 as a scaffolding protein . J. Biol. Chem. . 275 . 27 . 20578–87 . July 2000 . 10781592 . 10.1074/jbc.M001887200 . free .
- Zamora-Leon SP, Lee G, Davies P, Shafit-Zagardo B . Binding of Fyn to MAP-2c through an SH3 binding domain. Regulation of the interaction by ERK2 . J. Biol. Chem. . 276 . 43 . 39950–8 . October 2001 . 11546790 . 10.1074/jbc.M107807200 . free .
- Frappier T, Stetzkowski-Marden F, Pradel LA . Interaction domains of neurofilament light chain and brain spectrin . Biochem. J. . 275 . Pt 2 . 521–7 . April 1991 . 1902666 . 1150082 . 10.1042/bj2750521.
- Todorov PT, Hardisty RE, Brown SD . Myosin VIIA is specifically associated with calmodulin and microtubule-associated protein-2B (MAP-2B) . Biochem. J. . 354 . Pt 2 . 267–74 . March 2001 . 11171103 . 1221652 . 10.1042/0264-6021:3540267 .