The 18.5-kDa splice isoform of myelin basic protein (MBP) predominates in the adult brain, adhering the cytoplasmic leaflets of the oligodendrocyte membrane together, but also assembling the cytoskeleton at leading edges of membrane processes. Here, we characterized MBP's role as a microtubule-assembly protein (MAP). Using light scattering and sedimentation assays we found that pseudo-phosphorylation of Ser54 (murine 18.5-kDa sequence) significantly enhanced the rate but not the final degree of polymerization. This residue lies within a short KPGSG motif identical to one in tau, a ubiquitous MAP important in neuronal microtubule assembly. Using polypeptide constructs, each comprising one of three major amphipathic alpha-helical molecular recognition fragments of 18.5-kDa MBP, we identified the N-terminal alpha 1-peptide as sufficient to cause microtubule polymerization, the rate of which was significantly enhanced in the presence of dodecylphosphocholine (DPC) micelles to mimic a lipidic environment. (C) 2015 Elsevier Inc. All rights reserved.