Topic
Intermembrane transport
About: Intermembrane transport is a research topic. Over the lifetime, 14 publications have been published within this topic receiving 396 citations.
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TL;DR: The hypothesis is that the PLA(2), apart from its role in second messenger generation, might play a direct and general role in the vesiculation processes underlying the intermembrane transport of rafts through purely physicochemical mechanisms.
Abstract: Cellular processes involving membrane vesiculation are related to cellular transport and membrane components trafficking. Endocytosis, formation of caveolae and caveosomes, as well as Golgi membranes traffic have been linked to the existence and dynamics of particular types of lipid/protein membrane domains, enriched in sphingolipids and cholesterol, called rafts [Nature 387 (1997) 569; Trends Cell Biol. 12 (2002) 296; Biochemistry 27 (1988) 6197]. In addition, the participation of phospholipases in the vesiculation of Golgi and other membranes has been already established [Traffic 1 (2000) 504] essentially in their role in the production of second messenger molecules. In this work we illustrate with raft-containing giant lipid vesicles a mechanism for raft-vesicle expulsion from the membrane due to the activity of a single enzyme-phospholipase A2 (PLA2). This leads to the hypothesis that the PLA2, apart from its role in second messenger generation, might play a direct and general role in the vesiculation processes underlying the intermembrane transport of rafts through purely physicochemical mechanisms. These mechanisms would be: enzyme adsorption leading to membrane curvature generation (budding), and enzyme activity modulation of the line tension at the raft boundaries, which induces vesicle fission.
116 citations
TL;DR: Drug discovery aimed at regulating ER-to-mitochondria communication may open a new avenue in treatments of human diseases as recent studies have begun to unveil the importance of interorganelle communication in the innate immune response to virus infection and in the pathophysiology of neurodegenerative/neurodevelopmental disorders.
Abstract: The mitochondria-associated endoplasmic reticulum membrane (MAM) is a specialized subdomain of the endoplasmic reticulum (ER) membrane that regulates ER-mitochondria communications. The MAM is characterized by direct apposition to a mitochondrion, a unique lipid profile, and the expression of a unique set of proteins involved in Ca(2+) signaling, phospholipid biosynthesis, protein folding, and membrane tethering. The association of the MAM with a mitochondrion is in part cytoskeleton independent and dynamically changed by an elevation of the cytosolic Ca(2+) level. The mechanisms underlying the genesis of MAM are unclear but might involve COPI-dependent vesicular transport and soluble NSF attachment protein receptor. The MAM is recognized as a center for intermembrane transport of phospholipids and for direct Ca(2+) transmission to mitochondria that activates the tricarboxylic acid cycle. However, MAM might be also involved in the interorganelle transport of cholesterol, ceramides, ATP, and proteins as well as in proteasomal protein degradation and lipid droplet formation. Recent studies have begun to unveil the importance of interorganelle communication in the innate immune response to virus infection and in the pathophysiology of neurodegenerative/neurodevelopmental disorders. Thus, drug discovery aimed at regulating ER-to-mitochondria communication may open a new avenue in treatments of human diseases.
86 citations
TL;DR: Evidence is provided that biliary lecithin and cholesterol are derived from a microsomal subpool regulated by the flux of enterohepatic bile acids, and the role of the bile canalicular membranes with respect to biliary lipids is primarily transport rather than synthesis.
Abstract: The role of bile canalicular and microsomal membranes in the synthesis and transport of biliary lipids was investigated by using the isolated perfused rat liver model. Labeled lecithin precursors ((3H)-palmitic acid, (14C)linoleic acid, (3H)choline, and 32PO4) and a cholesterol precursor ((3H)mevalonic acid) were administered with and without sodium taurocholate. The incorporation pattern of these labeled precursors into linoleyl and arachidonyl lecithins and cholesterol fractions of microsomes, bile canaliculi, and bile were examined at 30-min intervals up to 90 min. Marker enzymes and electron microscopy indicated that isolated subfractions of plasma membranes were enriched with bile canaliculi (less than 10 percent microsomal contamination). Taurocholate significantly stimulated the incorporation of 32PO4, (3H)choline, (3H)palmitic acid, and (14C)linoleic acid into linoleyl and arachidonyl lecithin with parallel incorporation curves for microsomal and bile canalicular membranes throughout the 90-min study period. During the 30-60-min period, however, these same lecithin fractions in bile significantly exceeded the specific activity of the membrane lecithins. The enzyme CDP-choline diglyceride transferase was virtually absent from canaliculi relative to microsomes, indicating that canaliculi lack the capacity for de novo lecithin synthesis. Incorporation of (3H)mevalonic acid into membranous and biliary cholesterol followed a pattern similar to that for lecithin. These data provide evidence that (a) biliary lecithin and cholesterol are derived from a microsomal subpool regulated by the flux of enterohepatic bile acids, (b) the role of the bile canalicular membranes with respect to biliary lipids is primarily transport rather than synthesis, and (c) lecithin and cholesterol are transported together from microsomes to bile. The findings are consistent with the existence of a cytoplasmic lipid complex within the hepatocyte which is actively involved in the intermembrane transport of biliary lipid.
71 citations
TL;DR: This perspective addresses recent advances in lipid transport across the Gram-negative inner and outer membranes and lays out the evidence in an unbiased, yet critical, manner for Mla-mediated transport in addition to postulation of mechanisms for anterograde lipid transport from the inner to outer membranes.
Abstract: This perspective addresses recent advances in lipid transport across the Gram-negative inner and outer membranes. While we include a summary of previously existing literature regarding this topic, we focus on the maintenance of lipid asymmetry (Mla) pathway. Discovered in 2009 by the Silhavy group [J. C. Malinverni, T. J. Silhavy, Proc. Natl. Acad. Sci. U.S.A. 106, 8009–8014 (2009)], Mla has become increasingly appreciated for its role in bacterial cell envelope physiology. Through the work of many, we have gained an increasingly mechanistic understanding of the function of Mla via genetic, biochemical, and structural methods. Despite this, there is a degree of controversy surrounding the directionality in which Mla transports lipids. While the initial discovery and subsequent studies have posited that it mediated retrograde lipid transport (removing glycerophospholipids from the outer membrane and returning them to the inner membrane), others have asserted the opposite. This Perspective aims to lay out the evidence in an unbiased, yet critical, manner for Mla-mediated transport in addition to postulation of mechanisms for anterograde lipid transport from the inner to outer membranes.
44 citations
TL;DR: The diversity of lipids, methods to study intra- and inter-membrane lipid transport, and lipid transport processes are described, which are likely to provide both new research opportunities and rewards for those who tackle this long-standing problem of cell biology.
Abstract: Publisher Summary Lipid transport is a fundamental process essential to all cell growth, division, and differentiation This chapter describes the diversity of lipids, methods to study intra- and inter-membrane lipid transport, and lipid transport processes Various methods to study intra- and inter-membrane lipid transport, including fluorescent probes, spin-labeled analogs, a symmetric chemical modification of membranes, phospholipid transfer proteins, rapid plasma membrane isolation, and organelle-specific lipid metabolism The movement of lipids within the cell can be divided into two different general classes of transport: intramembrane transport and intermembrane transport The application of fluorescent probes continues to provide new insights and real time images of the selected aspects of lipid transport As the examination of these processes now begins to enter the realm of the manipulation of mutant cells, genes, and gene products, there remains much to be accomplished The current molecular tools, combined with new genetic strategies are likely to provide both new research opportunities and rewards for those who tackle this long-standing problem of cell biology
38 citations