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Journal of Neuroscience, Vol 15, 5753-5764, Copyright © 1995 by Society for Neuroscience
Characterization of a rat gene, rMAL, encoding a protein with four hydrophobic domains in central and peripheral myelin
N Schaeren-Wiemers, DM Valenzuela, M Frank and ME Schwab
Institute for Brain Research, University of Zurich, Switzerland.
Wrapping and compaction of myelin sheaths around axons require specific
membrane and membrane-associated proteins. Transmembrane proteins like
proteolipid protein (PLP), the peripheral myelin protein 22 (PMP-22) and P0
as well as myelin basic protein (MBP) are crucial for this process. We have
isolated a rat cDNA, initially denominated NS 3, that is mainly expressed
in the myelinating cells of the nervous system, the oligodendrocytes and
Schwann cells. The cDNA encodes a highly hydrophobic protein of 16.8 kDa
with four putative transmembrane domains. The 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 resembles the structure of gap junction proteins.
Sequence analysis showed that NS 3 is the rat homolog of a human gene
called MAL that was cloned from, and is expressed in various T-cell lines.
Therefore, we call this gene rMAL (rat MAL). In the nervous system, the
expression of rMAL, mRNA begins after birth and is highest during
myelination. In situ hybridization shows that rMAL mRNA is exclusively
expressed in white and gray matter oligodendrocytes in the CNS and in
myelinating Schwann cells in peripheral nerves. Immunohistochemistry using
a peptide-specific antibody localized the rMAL protein in the myelinated
areas of the CNS and PNS. Furthermore, we demonstrate by immunoblot
analysis that rMAL is a component of myelin. Its structure and distribution
suggest that the rMAL protein might play an important role in compact
myelin. We propose that the name rMAL protein refers to rat Myelin And
Lymphocyte protein.
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