title: MAP2c prevents arachidonic acid-induced fibril formation of tau: Role of chaperone activity and phosphorylation.
abstract: Tau has long been associated with Alzheimer's disease, where it forms neurofibrillary tangles. Here we show for the first time by electron microscopy that MAP2c prevents arachidonic acid-induced in vitro aggregation of tau. However, phosphorylated MAP2c failed to prevent the same. Previously we reported that MAP2c possesses chaperone-like activity while tau does not (Sarkar et al., 2004, Eur J Biochem., 271(8), 1488-96). Here we demonstrate that phosphorylation severely impaired the chaperone activity of MAP2c, implying a crucial role of chaperone in preventing tau fibrillation. Additionally, the ability of MAP2c to induce microtubule polymerization was abolished completely upon phosphorylation. As tau and MAP2c possess highly homologous C-termini, we speculated that the N-terminus of MAP2c might account for its chaperone activity. Nevertheless, experiments showed that N-terminus of MAP2c alone is inactive as a chaperone. Our preliminary findings suggest that MAP2c/MAP2 could be one of the regulators maintaining tau homeostasis in the cell.
authors.affiliation: Division of Molecular Medicine, Clinical Proteomics Unit, St John's Research Institute, St John's National Academy of Health Sciences, Koramangala, Bangalore 560034, India.
authors.forename: Gopa
authors.initials: G
authors.lastname: Mitra
authors.affiliation: Department of Biotechnology, Haldia Institute of Technology, East Midnapore, 721657, India.
authors.forename: Suvroma
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Biochemistry, Bose Institute, Centenary Campus, Calcutta 700054, India.
authors.forename: Asim
authors.initials: A
authors.lastname: Poddar
authors.affiliation: Department of Biochemistry, Bose Institute, Centenary Campus, Calcutta 700054, India. Electronic address: bablu@jcbose.ac.in.
authors.forename: Bhabatarak
authors.initials: B
authors.lastname: Bhattacharyya
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D066263:Protein Aggregation, Pathological / Q000139:chemically induced* / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D051381:Rats; D014404:Tubulin / Q000737:chemistry; D016875:tau Proteins / Q000737:chemistry*
chemical_list: C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D014404:Tubulin; D016875:tau Proteins; D016718:Arachidonic Acid; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
keywords: Alzheimer's disease; Chaperone; MAP2c; Phosphorylation; Tau