MAL, a proteolipid in glycosphingolipid enriched domains: functional implications in myelin and beyond.
The myelin and lymphocyte protein MAL (VIP17/MVP17) is a proteolipid of 17 kD with a hydrophobicity pattern that indicates a four transmembrane domain structure. The MAL cDNA has been cloned from human T-cells, rat oligodendrocytes and the Madin-Darby canine kidney (MDCK) cell line. In the nervous system both myelinating cells, oligodendrocytes and Schwann cells, express MAL protein. MAL expression parallels myelin formation, and MAL is predominantly localized in compact myelin. Prior to myelin formation MAL is also found in immature Schwann cells. Outside the nervous system MAL expression is found in T-cells and in distinct epithelial cells, e.g. in kidney, stomach and thyroid gland, where MAL is localised in the apical plasma membrane. Specific glycosphingolipids, e.g. galactosylceramide and sulfatide, are enriched in such apical kidney and stomach membranes as well as in myelin. MAL copurifies with these glycosphingolipids in detergent insoluble domains, indicating a close association and possible functional interactions of MAL with glycosphingolipids in these tissues. Moreover, recent reports point to additional functions of MAL-glycosphingolipid complexes in signalling, cell differentiation and apical sorting. The role of MAL in the formation, stabilisation and maintenance of glycosphingolipid-enriched membrane microdomains and its contribution to specific membrane properties in myelin and epithelial cells are discussed.
Frank
M
M
Brain Research Institute, Department of Neuromorphology, University of Zurich, Switzerland. frankm03@doc.mssm.edu
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D006028:Glycosphingolipids / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000378:metabolism; D026901:Membrane Transport Proteins; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D005810:Multigene Family; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000502:physiology*; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D011510:Proteolipids / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D006028:Glycosphingolipids; C569026:MAL protein, human; C569028:Mal protein, rat; D026901:Membrane Transport Proteins; D009185:Myelin Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D011510:Proteolipids