Biomaterial Database

Regulated Alternative Translocation: A Mechanism Regulating Transmembrane Proteins Through Topological Inversion. 2021

Jin Ye

Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA. Jin.ye@utsouthwestern.edu.

Transmembrane proteins must adopt a proper topology to execute their functions. In mammalian cells, a transmembrane protein is believed to adopt a fixed topology. This assumption has been challenged by recent reports that ceramide or related sphingolipids regulate some transmembrane proteins by inverting their topology. Ceramide inverts the topology of certain newly synthesized polytopic transmembrane proteins by altering the direction through which their first transmembrane helices are translocated across membranes. Thus, this regulatory mechanism has been designated as Regulated Alternative Translocation (RAT). The physiological importance of this topological regulation has been demonstrated by the finding that ceramide-induced RAT of TM4SF20 (Transmembrane 4 L6 family member 20) is crucial for the effectiveness of doxorubicin-based chemotherapy, and that dihydroceramide-induced RAT of CCR5 (C-C chemokine receptor type 5), a G protein-coupled receptor, is required for lipopolysaccharide (LPS) to inhibit chemotaxis of macrophages. These observations suggest that topological inversion through RAT could be an emerging mechanism to regulate transmembrane proteins.

UI	MeSH Term	Description	Entries
D008070	Lipopolysaccharides	Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)	Lipopolysaccharide,Lipoglycans
D008565	Membrane Proteins	Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.	Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013107	Sphingolipids	A class of membrane lipids that have a polar head and two nonpolar tails. They are composed of one molecule of the long-chain amino alcohol sphingosine (4-sphingenine) or one of its derivatives, one molecule of a long-chain acid, a polar head alcohol and sometimes phosphoric acid in diester linkage at the polar head group. (Lehninger et al, Principles of Biochemistry, 2nd ed)	Lysosphingolipids,Sphingolipid
D043562	Receptors, G-Protein-Coupled	The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.	G Protein Coupled Receptor,G-Protein-Coupled Receptor,G-Protein-Coupled Receptors,G Protein Coupled Receptors,Receptor, G-Protein-Coupled,Receptors, G Protein Coupled
D019713	Receptors, CCR5	CCR receptors with specificity for CHEMOKINE CCL3; CHEMOKINE CCL4; and CHEMOKINE CCL5. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; MACROPHAGES; MAST CELLS; and NK CELLS. The CCR5 receptor is used by the HUMAN IMMUNODEFICIENCY VIRUS to infect cells.	Antigens, CD195,CC Chemokine Receptor 5,CCR5 Receptors,CD195 Antigens,CC-CKR5,CCR5 Receptor,CKR5 Receptors,Receptors, CKR5,Receptor, CCR5