Alternative titles; symbols
HGNC Approved Gene Symbol: MAP2
Cytogenetic location: 2q34 Genomic coordinates (GRCh38): 2:209,424,047-209,734,112 (from NCBI)
Neve et al. (1986) identified a partial human cDNA for microtubule-associated protein-2.
By in situ hybridization with specific cDNA probes, Garner et al. (1988) showed that mRNA for dendrite-specific microtubule-associated protein MAP2 was present in dendrites in the developing brain. By contrast, the mRNA for tubulin (191120), a protein present in both axons and dendrites, was localized exclusively in neuronal cell bodies.
The microtubule-associated proteins (MAPs) isolated from brain coassemble with tubulin into microtubules in vitro. MAP2, a 280-kD protein, is highly concentrated in neuronal somata and dendrites. Kindler and Garner (1994) noted that MAP2 can be resolved by SDS-PAGE into at least 3 isoforms. The 280-kD MAP2B is present throughout rat brain development, and the slightly larger MAP2A appears first during the end of the second week of postnatal life. MAP2C is composed of several bands of about 70 kD, is present during early brain development, and largely disappears from the mature brain except for the retina, olfactory bulb, and cerebellum. MAP2A and MAP2B are encoded by 9-kb mRNAs, and MAP2C by a 6-kb transcript.
Kindler and Garner (1994) described the isolation and nucleotide sequence of human and rat cDNA clones encoding both high and low molecular weight MAP2 variants which contained either 3 or 4 tandem repeats in their microtubular binding domains. Each repeat was predicted to encode a 31-amino acid residue consisting of a highly conserved 18-amino acid residue 'repeat core' flanked by less conserved spacer sequences.
Pregnenolone (PREG) and a synthetic analog, MePREG, bind to MAP2 and stimulate microtubule polymerization. Fontaine-Lenoir et al. (2006) found that PREG, MePREG, and progesterone (PROG), the metabolite of PREG, significantly enhanced neurite outgrowth of NGF (see NGFB; 162030)-treated rat PC12 pheochromocytoma cells. Map2 RNA interference prevented the stimulatory effect of PREG and MePREG, but not PROG, on neurite extension. Fontaine-Lenoir et al. (2006) concluded that MAP2 is a specific PREG and MePREG receptor.
Kalcheva et al. (1995) determined that the MAP2 gene contains 19 exons. The authors found that alternative splicing of coding exons generated a great diversity of MAP2 transcripts and isoforms.
Neve et al. (1986) determined the chromosomal localization of the MAP2 gene by spot-blot mapping of DNA from flow-sorted metaphase chromosomes and by in situ hybridization. They concluded that the MAP2 gene is located in segment 2q34-q35.
Pescucci et al. (2003) found a large deletion of 2q encompassing the MAP2 gene in a 14-year-old female with autism and some features suggesting Rett syndrome (312750). Like a Rett patient, she was dyspraxic and showed frequent hand-washing stereotypic activities, hyperpnea, and bruxism. As in the 'preserved speech variant' (PSV) of Rett syndrome, she was obese, able to speak in second and third persons, frequently echolalic, and had normal head circumference and autistic behavior. In addition, she had dysmorphic features including downslanting palpebral fissures, low-set ears without lobuli, bilateral flat feet, and bilateral syndactyly in the second and third toes, which do not belong to the spectrum of manifestations in Rett syndrome. Her MECP2 gene (300005) was intact. Her de novo 2q34 deletion was of paternal origin. The deleted region was shown to contain 33 known and 14 putative genes. Because alteration of neuronal maturation, dendritic anomalies, and a decrease in MAP2 immunoreactivity in white matter neurons are well documented in Rett syndrome, Pescucci et al. (2003) proposed MAP2 as a good candidate for the basis of the PSV phenotype in this patient.
Marsden et al. (1996) produced transgenic mice that overexpressed embryonic Map2 (referred to by them as MAP2c) without inducing detectable effects on the morphology of neurons. The transgenic MAP2c was present in dendrites but not in axons, and transgenic MAP2c mRNA was limited to cell bodies. The authors concluded that the dendritic localization of MAP2c protein is not the result of previous transport of its mRNA but rather depends on a signal associated with the protein itself.
Chang et al. (2003) found progressive demyelination and progressive loss of microtubules within axons and dendrites of Jnk1 (MAPK8; 601158)-null mouse spinal cord, neocortex, and hippocampus. They determined that the loss of microtubules was due to hypophosphorylation of Map2, which reduced the ability of Map2 to bind microtubules and promote tubulin polymerization.
Chang, L., Jones, Y., Ellisman, M. H., Goldstein, L. S. B., Karin, M. JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins. Dev. Cell 4: 521-533, 2003. [PubMed: 12689591] [Full Text: https://doi.org/10.1016/s1534-5807(03)00094-7]
Fontaine-Lenoir, V., Chambraud, B., Fellous, A., David, S., Duchossoy, Y., Baulieu, E.-E., Robel, P. Microtubule-associated protein 2 (MAP2) is a neurosteroid receptor. Proc. Nat. Acad. Sci. 103: 4711-4716, 2006. [PubMed: 16537405] [Full Text: https://doi.org/10.1073/pnas.0600113103]
Garner, C. C., Tucker, R. P., Matus, A. Selective localization of messenger RNA for cytoskeletal protein MAP2 in dendrites. Nature 336: 674-677, 1988. [PubMed: 3200318] [Full Text: https://doi.org/10.1038/336674a0]
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. Nat. Acad. Sci. 92: 10894-10898, 1995. [PubMed: 7479905] [Full Text: https://doi.org/10.1073/pnas.92.24.10894]
Kindler, S., Garner, C. C. Four repeat MAP2 isoforms in human and rat brain. Molec. Brain Res. 26: 218-224, 1994. [PubMed: 7854050] [Full Text: https://doi.org/10.1016/0169-328x(94)90093-0]
Marsden, K. M., Doll, T., Ferralli, J., Botteri, F., Matus, A. Transgenic expression of embryonic MAP2 in adult mouse brain: implications for neuronal polarization. J. Neurosci. 16: 3265-3273, 1996. [PubMed: 8627364] [Full Text: https://doi.org/10.1523/JNEUROSCI.16-10-03265.1996]
Neve, R. L., Harris, P., Kosik, K. S., Kurnit, D. M., Donlon, T. A. 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: 271-280, 1986. [PubMed: 3103857] [Full Text: https://doi.org/10.1016/0169-328x(86)90033-1]
Pescucci, C., Meloni, I., Bruttini, M., Ariani, F., Longo, I., Mari, F., Canitano, R., Hayek, G., Zappella, M., Renieri, A. Chromosome 2 deletion encompassing the MAP2 gene in a patient with autism and Rett-like syndrome. Clin. Genet. 64: 497-501, 2003. [PubMed: 14986829] [Full Text: https://doi.org/10.1046/j.1399-0004.2003.00176.x]