title: MAL, but not MAL2, expression promotes the formation of cholesterol-dependent membrane domains that recruit apical proteins.
abstract: Our recent studies have been aimed at understanding the mechanisms regulating apical protein sorting in polarized epithelial cells. In particular, we have been investigating how lipid rafts serve to sort apical proteins in the biosynthetic pathway. The recent findings that lipid domains are too small or transient to host apically destined cargo have led to newer versions of the hypothesis that invoke proteins required for lipid domain coalescence and stabilization. MAL (myelin and lymphocyte protein) and its highly conserved family member, MAL2, have emerged as possible regulators of this process in the direct and indirect apical trafficking pathways respectively. To test this possibility, we took a biochemical approach. We determined that MAL, but not MAL2, self-associates, forms higher-order cholesterol-dependent complexes with apical proteins and promotes the formation of detergent-resistant membranes that recruit apical proteins. Such biochemical properties are consistent with a role for MAL in raft coalescence and stabilization. These findings also support a model whereby hydrophobic mismatch between the long membrane-spanning helices of MAL and the short-acyl-chain phospholipids in the Golgi drive formation of lipid domains rich in raft components that are characterized by a thicker hydrophobic core to alleviate mismatch.
authors: Department of Biology, The Catholic University of America, NE, Washington, DC 20064, U.S.A.
authors: Sai P
authors: SP
authors: Ramnarayanan
authors: Pamela L
authors: PL
authors: Tuma
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000737:chemistry / Q000502:physiology*; D005786:Gene Expression Regulation; D021962:Membrane Microdomains / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009185:Myelin Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D017434:Protein Structure, Tertiary / Q000235:genetics; D011510:Proteolipids / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051381:Rats; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: C569026:MAL protein, human; C438606:MAL2 protein, human; C569028:Mal protein, rat; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009185:Myelin Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D011510:Proteolipids; D033921:Vesicular Transport Proteins; D002784:Cholesterol