scholarly journals Mechanisms of nonvesicular lipid transport

2021 ◽  
Vol 220 (3) ◽  
Author(s):  
Karin M. Reinisch ◽  
William A. Prinz
Keyword(s):  
High Volume ◽  
Lipid Transport ◽  
Lipid Transfer ◽  
Specific Lipids ◽  
Membrane Contact Sites ◽  
Membrane Contact ◽  
Transfer Mechanisms ◽  
Efficient Transfer

We have long known that lipids traffic between cellular membranes via vesicles but have only recently appreciated the role of nonvesicular lipid transport. Nonvesicular transport can be high volume, supporting biogenesis of rapidly expanding membranes, or more targeted and precise, allowing cells to rapidly alter levels of specific lipids in membranes. Most such transport probably occurs at membrane contact sites, where organelles are closely apposed, and requires lipid transport proteins (LTPs), which solubilize lipids to shield them from the aqueous phase during their transport between membranes. Some LTPs are cup like and shuttle lipid monomers between membranes. Others form conduits allowing lipid flow between membranes. This review describes what we know about nonvesicular lipid transfer mechanisms while also identifying many remaining unknowns: How do LTPs facilitate lipid movement from and into membranes, do LTPs require accessory proteins for efficient transfer in vivo, and how is directionality of transport determined?

scholarly journals Biogenesis of RNA-containing extracellular vesicles at endoplasmic reticulum membrane contact sites

2020 ◽  
Author(s):  
Bahnisikha Barman ◽  
Jie Ping ◽  
Evan Krystofiak ◽  
Ryan Allen ◽  
Nripesh Prasad ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Extracellular Vesicles ◽  
Rna Binding ◽  
Lipid Analysis ◽  
Tumor Formation ◽  
Endoplasmic Reticulum Membrane ◽  
Lipid Transfer ◽  
Membrane Contact Sites ◽  
Membrane Contact

SummaryRNA transferred via extracellular vesicles (EVs) can influence cell and tissue phenotypes; however, the biogenesis of RNA-containing EVs is poorly understood and even controversial. Here, we identify the conserved endoplasmic reticulum membrane contact site (MCS) linker protein VAP-A as a major regulator of the RNA and RNA-binding protein content of small and large EVs. We also identify a unique subpopulation of secreted small EVs that is highly enriched in RNA and regulated by VAP-A. Functional experiments revealed that VAP-A-regulated EVs are critical for the transfer of miR-100 between cells and for in vivo tumor formation. Lipid analysis of VAP-A-knockdown EVs revealed large alterations in lipids known to regulate EV biogenesis, including ceramides and cholesterol. Knockdown of VAP-A-binding ceramide and cholesterol transfer proteins CERT and ORP1L led to similar defects in biogenesis of RNA-containing EVs. We propose that lipid transfer at VAP-A-positive MCS drives biogenesis of a select RNA-containing EV population.

scholarly journals Membrane Contact Sites: Complex Zones for Membrane Association and Lipid Exchange

2015 ◽  
Vol 8s1 ◽  
pp. LPI.S37190 ◽  
Author(s):  
Evan Quon ◽  
Christopher T. Beh
Keyword(s):  
Membrane Association ◽  
Ion Transfer ◽  
Lipid Transfer ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Protein Carriers ◽  
Lipid Exchange ◽  
Membrane Tethering ◽  
Membrane Contact

Lipid transport between membranes within cells involves vesicle and protein carriers, but as agents of nonvesicular lipid transfer, the role of membrane contact sites has received increasing attention. As zones for lipid metabolism and exchange, various membrane contact sites mediate direct associations between different organelles. In particular, membrane contact sites linking the plasma membrane (PM) and the endoplasmic reticulum (ER) represent important regulators of lipid and ion transfer. In yeast, cortical ER is stapled to the PM through membrane-tethering proteins, which establish a direct connection between the membranes. In this review, we consider passive and facilitated models for lipid transfer at PM–ER contact sites. Besides the tethering proteins, we examine the roles of an additional repertoire of lipid and protein regulators that prime and propagate PM–ER membrane association. We conclude that instead of being simple mediators of membrane association, regulatory components of membrane contact sites have complex and multilayered functions.

scholarly journals Functions of Oxysterol-Binding Proteins at Membrane Contact Sites and Their Control by Phosphoinositide Metabolism

2021 ◽  
Vol 9 ◽  
Author(s):  
Fubito Nakatsu ◽  
Asami Kawasaki
Keyword(s):  
Lipid Transport ◽  
Phosphoinositide Metabolism ◽  
Lipid Transfer ◽  
Cellular Functions ◽  
Characteristic Functional ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Tightly Coupled ◽  
Membrane Contact ◽  
The Right

Lipids must be correctly transported within the cell to the right place at the right time in order to be fully functional. Non-vesicular lipid transport is mediated by so-called lipid transfer proteins (LTPs), which contain a hydrophobic cavity that sequesters lipid molecules. Oxysterol-binding protein (OSBP)-related proteins (ORPs) are a family of LTPs known to harbor lipid ligands, such as cholesterol and phospholipids. ORPs act as a sensor or transporter of those lipid ligands at membrane contact sites (MCSs) where two different cellular membranes are closely apposed. In particular, a characteristic functional property of ORPs is their role as a lipid exchanger. ORPs mediate counter-directional transport of two different lipid ligands at MCSs. Several, but not all, ORPs transport their lipid ligand from the endoplasmic reticulum (ER) in exchange for phosphatidylinositol 4-phosphate (PI4P), the other ligand, on apposed membranes. This ORP-mediated lipid “countertransport” is driven by the concentration gradient of PI4P between membranes, which is generated by its kinases and phosphatases. In this review, we will discuss how ORP function is tightly coupled to metabolism of phosphoinositides such as PI4P. Recent progress on the role of ORP-mediated lipid transport/countertransport at multiple MCSs in cellular functions will be also discussed.

Non-vesicular lipid trafficking at the endoplasmic reticulum–mitochondria interface

2018 ◽  
Vol 46 (2) ◽  
pp. 437-452 ◽  
Author(s):  
Francesca Giordano
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Transport ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Transport Pathways ◽  
Lipid Trafficking ◽  
Cellular Processes ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact

Mitochondria are highly dynamic organelles involved in various cellular processes such as energy production, regulation of calcium homeostasis, lipid trafficking, and apoptosis. To fulfill all these functions and preserve their morphology and dynamic behavior, mitochondria need to maintain a defined protein and lipid composition in both their membranes. The maintenance of mitochondrial membrane identity requires a selective and regulated transport of specific lipids from/to the endoplasmic reticulum (ER) and across the mitochondria outer and inner membranes. Since they are not integrated in the classical vesicular trafficking routes, mitochondria exchange lipids with the ER at sites of close apposition called membrane contact sites. Deregulation of such transport activities results in several pathologies including cancer and neurodegenerative disorders. However, we are just starting to understand the function of ER–mitochondria contact sites in lipid transport, what are the proteins involved and how they are regulated. In this review, we summarize recent insights into lipid transport pathways at the ER–mitochondria interface and discuss the implication of recently identified lipid transfer proteins in these processes.

scholarly journals A programmable DNA-origami platform for studying protein-mediated lipid transfer between bilayers

2019 ◽  
Author(s):  
Xin Bian ◽  
Zhao Zhang ◽  
Pietro De Camilli ◽  
Chenxiang Lin
Keyword(s):  
Dna Origami ◽  
Lipid Transport ◽  
Dna Nanostructures ◽  
Lipid Transfer ◽  
Membrane Contact Sites ◽  
Mechanistic Insight ◽  
Donor And Acceptor ◽  
Membrane Contact ◽  
Insight Into

AbstractNon-vesicular lipid transport between bilayers at membrane contact sites plays important physiological roles. Mechanistic insight into the action of lipid transport proteins localized at these sites (bridge/tunnel versus shuttle models) requires a determination of the distance between bilayers at which this transport can occur. Here, we developed DNA-origami nanostructures to organize size-defined liposomes at precise distances and used them to study lipid transfer by the SMP domain of E-Syt1. Pairs of DNA ring-templated donor and acceptor liposomes were docked through DNA pillars, which determined their distance. The SMP domain was anchored to donor liposomes via an unstructured linker and lipid transfer was assessed via a FRET-based assay. We show that lipid transfer can occur over distances that exceed the length of SMP dimer, compatible with a shuttle model. The DNA nanostructures developed here can be adapted to study other processes occurring where two membranes are closely apposed to each other.

scholarly journals Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells

2019 ◽  
Vol 77 (14) ◽  
pp. 2839-2857 ◽  
Author(s):  
Elsa Meneses-Salas ◽  
Ana García-Melero ◽  
Kristiina Kanerva ◽  
Patricia Blanco-Muñoz ◽  
Frederic Morales-Paytuvi ◽  
...  
Keyword(s):  
Late Endosome ◽  
Dependent Manner ◽  
Lipid Transfer ◽  
Cholesterol Accumulation ◽  
Membrane Contact Sites ◽  
Late Endosomes ◽  
Membrane Contact ◽  
Domain 3 ◽  
Niemann Pick ◽  
Mutant Cells

Abstract Cholesterol accumulation in late endosomes is a prevailing phenotype of Niemann-Pick type C1 (NPC1) mutant cells. Likewise, annexin A6 (AnxA6) overexpression induces a phenotype reminiscent of NPC1 mutant cells. Here, we demonstrate that this cellular cholesterol imbalance is due to AnxA6 promoting Rab7 inactivation via TBC1D15, a Rab7-GAP. In NPC1 mutant cells, AnxA6 depletion and eventual Rab7 activation was associated with peripheral distribution and increased mobility of late endosomes. This was accompanied by an enhanced lipid accumulation in lipid droplets in an acyl-CoA:cholesterol acyltransferase (ACAT)-dependent manner. Moreover, in AnxA6-deficient NPC1 mutant cells, Rab7-mediated rescue of late endosome-cholesterol export required the StAR-related lipid transfer domain-3 (StARD3) protein. Electron microscopy revealed a significant increase of membrane contact sites (MCS) between late endosomes and ER in NPC1 mutant cells lacking AnxA6, suggesting late endosome-cholesterol transfer to the ER via Rab7 and StARD3-dependent MCS formation. This study identifies AnxA6 as a novel gatekeeper that controls cellular distribution of late endosome-cholesterol via regulation of a Rab7-GAP and MCS formation.

Sign in / Sign up

Export Citation Format

Share Document