START ships lipids across interorganelle space.
The family of StAR related lipid transfer proteins (START) is so-named based on the distinctive capacity for these proteins to transport lipids between membranes. The START domain is a module of about 210 residues, which binds lipids such as glycerolipids, sphingolipids and sterols. This domain has a deep lipid-binding pocket - which shields the hydrophic ligand from the external aqueous environment - covered by a lid. Based on their homology, the fifteen START proteins in mammals have been allocated to six distinct subfamilies, each subfamily being more specialized in the transport and/or sensing of a lipid ligand species. However within the same subgroup, their expression profile and their subcellular localization distinguish them and are critical for their different biological functions. Indeed, START proteins act in a variety of distinct physiological processes, such as lipid transfer between intracellular compartments, lipid metabolism and modulation of signaling events. Mutation or deregulated expression of START proteins is linked to pathological processes, including genetic disorders, autoimmune diseases and cancers. Besides the common single START domain, which is always located at the carboxy-terminal end in mammals, most START proteins harbor additional domains predicted to be critical in favoring lipid exchange. Evidence from well characterized START proteins indicates that these additional domains might be tethering machineries able to bring distinct organelles together and create membrane contact sites prone to lipid exchange via the START domain.
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), UMR 7104 CNRS/U964 INSERM/Université de Strasbourg, BP10142, Illkirch, 67404 C.U. de Strasbourg, France. Electronic address: Fabien.Alpy@igbmc.fr.
Fabien
F
Alpy
Catherine
C
Tomasetto
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001692:Biological Transport; D002518:Ceramides / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D026901:Membrane Transport Proteins / Q000502:physiology*; D015388:Organelles / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding
D001647:Bile Acids and Salts; D002518:Ceramides; D026901:Membrane Transport Proteins; D010743:Phospholipids; D002784:Cholesterol
Lipid metabolism; Lipid transfer protein; Non-vesicular lipid transfer; START: (steroidogenic acute regulatory protein) related lipid transfer