Induction of microtubule-associated protein 1B expression in Schwann cells during nerve regeneration.

ABSTRACT

Microtubule-associated protein 1B (MAP1B) is expressed at high levels during development of the nervous system and is localized primarily in neurons while specific phosphorylated isoforms of MAP1B are localized exclusively in growing axons. The levels of MAP1B are down regulated in most regions of the adult CNS, but remain high in neurons and axons of the PNS. This study demonstrates that the expression of MAP1B is induced in adult Schwann cells following sciatic nerve lesion and regeneration. High levels of both mRNA and the MAP1B protein were detected in Schwann cells associated with the axotomized distal stump. Expression of MAP1B was also observed in cultured primary Schwann cells from neonatal rats. The properties of the MAP1B protein in cultured Schwann cells were further characterized by Western blot analysis using specific antibodies that recognize the N-terminal, middle and C-terminal domains of MAP1B. All of these antibodies detected a protein of 320-340 kDa demonstrating that MAP1B expressed by Schwann cells is very similar, or identical, to MAP1B expressed by neurons. The phosphorylation of MAP1B in Schwann cells was also studied using monoclonal antibodies (mAb) that recognize specific phosphorylation epitopes. The results indicated that the expression of MAP1B in Schwann cells exhibited a differential phosphorylation state that was recognized by mAb 1B6 but not by other mAbs, including 1B-P, 150 and RT97, that recognize phosphorylated MAP1B in growing axons. We therefore conclude that MAP1B is expressed in Schwann cells during both development and axonal regeneration, suggesting that the developmental pattern of MAP1B in these cells is recapitulated in adult Schwann cells during the early stages of regeneration and remyelination of injured peripheral axons. The presence of MAP1B in Schwann cells may support morphological changes of these cells, particularly the formation of processes prior to their differentiation into myelin forming Schwann cells.