The Tau of Myelin Basic Protein (MBP): Biophysical Studies of Microtubule Assembly by MBP

Abstract

Myelin basic proteins (MBP) are essential for the development and maintenance of healthy central nervous system myelin, amongst which the "classic" 18.5-kDa size isoform predominates in adults and is a candidate auto-antigen in the neurodegenerative disease Multiple Sclerosis. MBP is intrinsically disordered, and has many cellular partners, including the cytoskeletal component tubulin. These interactions have been shown to be mediated by combinatorial post-translational modifications (PTMs) that are altered throughout development and are aberrant during disease progression. This work further delineates MBP's 'dynamic molecular barcode' by characterizing the effect of PTMs on MBP's ability to assemble and stabilize MTs. A putative interacting domain is identified and probed using a combination of biochemical and biophysical techniques. This work contributes to our understanding of the underlying architecture of oligodendrocyte myelin, and enhances our conceptual framework of MBP's rich functional repertoire as a myelin protein, both in healthy and diseased states.