CHARACTERIZATION OF A RAT GENE, RMAL, ENCODING A PROTEIN WITH 4 HYDROPHOBIC DOMAINS IN CENTRAL AND PERIPHERAL MYELIN

Wrapping and compaction of myelin sheaths around axons require specifi c membrane and membrane-associated proteins. Transmembrane proteins li ke proteolipid protein (PLP), the peripheral myelin protein 22 (PMP-22 ) and P-0 as well as myelin basic protein (MBP) are crucial for this p rocess. We have isolated a rat cDNA, initially denominated NS 3, that is mainly expressed in the myelinating cells of the nervous system, th e oligodendrocytes and Schwann cells. The cDNA encodes a highly hydrop hobic protein of 16.8 kDa with four putative transmembrane domains. Th e putative NS 3 protein lacks a N-terminal hydrophobic leader sequence and has no consensus sequence for N-linked glycosylation. In contrast to PLP and PMP-22, the first and third putative transmembrane domain of the NS 3 protein contain charged amino acids, a feature which resem bles the structure of gap junction proteins. Sequence analysis showed that NS 3 is the rat homolog of a human gene called MAL that was clone d from, and is expressed in various T-cell lines. Therefore, we call t his gene rMAL (rat MAL). In the nervous system, the expression of rMAL , mRNA begins after birth and is highest during myelination. In situ h ybridization shows that rMAL mRNA is exclusively expressed in white an d gray matter oligodendrocytes in the CNS and in myelinating Schwann c ells in peripheral nerves. Immunohistochemistry using a peptide-specif ic antibody localized the rMAL protein in the myelinated areas of the CNS and PNS. Furthermore, we demonstrate by immunoblot analysis that r MAL is a component of myelin. Its structure and distribution suggest t hat the rMAL protein might play an important role in compact myelin. W e propose that the name rMAL protein refers to rat Myelin And Lymphocy te protein.