Characterization of a rat gene, rMAL, encoding a protein with four hydrophobic domains in central and peripheral myelin

Abstract

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.

Rafts in oligodendrocytes: Evidence and structure–function relationship

“…MAL is a 17 kDa non-glycosylated integral membrane protein that localizes in the Golgi (Puertollano et al, 1999) and is required for apical targeting in epithial cells (Cheong et al, 1999;Martin-Belmonte et al, 2000;Puertollano et al, 1999). In OLGs, MAL has been shown to be a component of GSL-rafts (Frank et al, 1998;Frank, 2000;Kim et al, 1995;Kim and Pfeiffer, 2002;Schaeren-Wiemers et al, 1995) and to end up in compact myelin (Frank et al, 1998). MAL is upregulated during active myelination (Kim et al, 1995;Schaeren-Wiemers et al, 1995).…”

“…In OLGs, MAL has been shown to be a component of GSL-rafts (Frank et al, 1998;Frank, 2000;Kim et al, 1995;Kim and Pfeiffer, 2002;Schaeren-Wiemers et al, 1995) and to end up in compact myelin (Frank et al, 1998). MAL is upregulated during active myelination (Kim et al, 1995;Schaeren-Wiemers et al, 1995). In addition, MAL can form oligomers, which might function to cluster rafts at the sites at which sorting takes place (Schuck and Simons, 2004).…”

Interleukin 4–induced gene 1 is activated in primary mediastinal large B-cell lymphoma

“…The MAL gene is normally expressed in lymphoid T cells, polarized epithelial cells, and myelin-forming cells. [17][18][19] It encodes a proteolipid believed to participate in membrane microdomains stabilization, intracellular transport, and signaling. 20,21 Its expression in PMBL may modify raft dynamics and contribute to neoplastic transformation.…”

VIP17/MAL, a lipid raft-associated protein, is involved in apical transport in MDCK cells

“…The canine VIP17 turned out to be a tetraspan membrane protein, almost identical to the human MAL, a protein identified as a marker of T cell maturation (22). This protein has a narrow tissue distribution, being present only in kidney, spinal cord, brain, the stomach, and the caecum of the large intestine (23)(24)(25). During differentiation of oligodendrocytes, VIP17/ MAL is expressed concomitantly to the rise in myelin production (23,24).…”