Amado Carreras-Sureda, Christopher Henry, Nicolas Demaurex
{"title":"Extending the Contacts Breaks the Flow.","authors":"Amado Carreras-Sureda, Christopher Henry, Nicolas Demaurex","doi":"10.1177/25152564221125045","DOIUrl":"https://doi.org/10.1177/25152564221125045","url":null,"abstract":"<p><p>In this news and views, we discuss our recent publication where we described how ER-PM membrane contact sites (MCS) are modulated during store operated calcium entry (SOCE). We also examine why enforcing ER-PM MCS by tethering proteins does not not enhance, but rather inhibits SOCE.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"6 ","pages":"25152564221125045"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9e/b4/10.1177_25152564221125045.PMC10243554.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10291752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Organization and Function of the Phagophore-ER Membrane Contact Sites.","authors":"Prado Vargas Duarte, Fulvio Reggiori","doi":"10.1177/25152564231183898","DOIUrl":"https://doi.org/10.1177/25152564231183898","url":null,"abstract":"<p><p>Macroautophagy is characterized by the <i>de novo</i> formation of double-membrane vesicles termed autophagosomes. The precursor structure of autophagosomes is a membrane cistern called phagophore, which elongates through a massive acquisition of lipids until closure. The phagophore establishes membrane-contact sites (MCSs) with the endoplasmic reticulum (ER), where conserved ATG proteins belonging to the ATG9 lipid scramblase, ATG2 lipid transfer and Atg18/WIPI4 β-propeller families concentrate. Several recent <i>in vivo</i> and <i>in vitro</i> studies have uncovered the relevance of these proteins and MCSs in the lipid supply required for autophagosome formation. Although important conceptual advances have been reached, the functional interrelationship between ATG9, ATG2 and Atg18/WIPI4 proteins at the phagophore-ER MCSs and their role in the phagophore expansion are not completely understood. In this review, we describe the current knowledge about the structure, interactions, localizations, and molecular functions of these proteins, with a particular emphasis on the yeast <i>Saccharomyces cerevisiae</i> and mammalian systems.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"6 ","pages":"25152564231183898"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6c/f5/10.1177_25152564231183898.PMC10350784.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10648390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mélody Subra, Zoé Grimanelli, Romain Gautier, Bruno Mesmin
{"title":"<i>Stranger Twins</i>: A Tale of Resemblance and Contrast Between VAP Proteins.","authors":"Mélody Subra, Zoé Grimanelli, Romain Gautier, Bruno Mesmin","doi":"10.1177/25152564231183897","DOIUrl":"https://doi.org/10.1177/25152564231183897","url":null,"abstract":"<p><p>When considering the vesicle-associated membrane protein-associated protein (VAP) family, major receptors at the surface of the endoplasmic reticulum (ER), it appears that VAP-A and VAP-B paralogs largely overlap in structure and function, and that specific features to distinguish these two proteins hardly exist or are poorly documented. Here, we question the degree of redundancy between VAP-A and VAP-B: is one simply a backup plan, in case of loss of function of one of the two genes, or are there molecular and functional divergences that would explain their maintenance during evolution?</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"6 ","pages":"25152564231183897"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/22/26/10.1177_25152564231183897.PMC10345920.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10353102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuliang Chen, Melissa A Roberts, Chun-Yuan Chen, Sebastian Markmiller, Hong-Guang Wei, Gene W Yeo, James G Granneman, James A Olzmann, Susan Ferro-Novick
{"title":"VPS13A and VPS13C Influence Lipid Droplet Abundance.","authors":"Shuliang Chen, Melissa A Roberts, Chun-Yuan Chen, Sebastian Markmiller, Hong-Guang Wei, Gene W Yeo, James G Granneman, James A Olzmann, Susan Ferro-Novick","doi":"10.1177/25152564221125613","DOIUrl":"10.1177/25152564221125613","url":null,"abstract":"<p><p>Lipid transfer proteins mediate the exchange of lipids between closely apposed membranes at organelle contact sites and play key roles in lipid metabolism, membrane homeostasis, and cellular signaling. A recently discovered novel family of lipid transfer proteins, which includes the VPS13 proteins (VPS13A-D), adopt a rod-like bridge conformation with an extended hydrophobic groove that enables the bulk transfer of membrane lipids for membrane growth. Loss of function mutations in VPS13A and VPS13C cause chorea acanthocytosis and Parkinson's disease, respectively. VPS13A and VPS13C localize to multiple organelle contact sites, including endoplasmic reticulum (ER) - lipid droplet (LD) contact sites, but the functional roles of these proteins in LD regulation remains mostly unexplored. Here we employ CRISPR-Cas9 genome editing to generate VPS13A and VPS13C knockout cell lines in U-2 OS cells via deletion of exon 2 and introduction of an early frameshift. Analysis of LD content in these cell lines revealed that loss of either VPS13A or VPS13C results in reduced LD abundance under oleate-stimulated conditions. These data implicate two lipid transfer proteins, VPS13A and VPS13C, in LD regulation.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"5 ","pages":"25152564221125613"},"PeriodicalIF":0.0,"publicationDate":"2022-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9703031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arun T John Peter, Ngaam J Cheung, Benoît Kornmann
{"title":"Csf1: A Putative Lipid Transport Protein Required for Homeoviscous Adaptation of the Lipidome.","authors":"Arun T John Peter, Ngaam J Cheung, Benoît Kornmann","doi":"10.1177/25152564221101974","DOIUrl":"10.1177/25152564221101974","url":null,"abstract":"<p><p>The non-vesicular transport of lipids between organelles mediated by lipid transport proteins (LTPs) is a key determinant of organelle biogenesis and function. Despite performing a vital function in organelle homeostasis, none of the LTP-encoding genes identified so far are truly essential, even in the simple genome of yeast, suggesting widespread redundancy. In line with this fact, it has been found that a number of LTPs have overlapping functions, making it challenging to assign unique roles for an individual LTP in lipid distribution. In our genetic screens under stringent conditions in which the distinct function of an LTP might become essential, we stumbled upon Csf1, a highly conserved protein with a Chorein-N motif found in other lipid transporters and unraveled a new function for Csf1 in lipid remodeling and homeoviscous adaptation of the lipidome. Here, we further speculate on the potential mechanisms of how the putative function of Csf1 in lipid transport could be intimately connected to its role in lipid remodeling across organelles.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"5 ","pages":"25152564221101974"},"PeriodicalIF":0.0,"publicationDate":"2022-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10298549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Moving Lipids, by the Numbers.","authors":"Pascal F Egea","doi":"10.1177/25152564221103080","DOIUrl":"https://doi.org/10.1177/25152564221103080","url":null,"abstract":"Lipid trafficking in eukaryotic cells can follow vesicular and non-vesicular pathways (Antonny et al., 2018). However, some organelles do rely exclusively on non-vesicular trafficking to obtain or distribute some of the lipids essential to their functions and biogenesis. In the past decades membrane contact sites between organelles have emerged as hubs for the non-vesicular trafficking of lipids, highlighting the importance of lipid transfer proteins (LTPs), a large functional class of structurally diverse proteins involved in this process (Egea, 2021).","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"5 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/13/10.1177_25152564221103080.PMC9484574.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9175646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The PH-like Domain of VPS13 Proteins - a Determinant of Localization to the Golgi Apparatus or to the Plasma Membrane.","authors":"Joanna Kaminska","doi":"10.1177/25152564221106024","DOIUrl":"https://doi.org/10.1177/25152564221106024","url":null,"abstract":"<p><p>Mutations in the four human genes <i>VPS13A-D</i>, encoding vacuolar protein sorting 13 (VPS13A-D) proteins, result in developmental or neurodegenerative diseases. Understanding the functioning of VPS13 proteins in physiology and pathology is a hot topic of research. Especially interesting is how VPS13 proteins are localized to specific membrane contact sites and function in lipid transport. Recently, the C-terminal Pleckstrin Homology (PH)-like domains of yeast Vps13 and human VPS13A were found to bind Arf1 GTPase and to phosphoinositol 4,5-bisphosphate. Here, hypotheses on the importance of the dual binding ability of the PH-like domain of VPS13A protein for cell physiology are presented. While yeast Vps13, together with Arf1 GTPase, is important for protein sorting in the Trans Golgi Network (TGN), the localization of VPS13A in TGN is speculated to restrict the binding of VPS13A to the plasma membrane.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"5 ","pages":"25152564221106024"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e3/f7/10.1177_25152564221106024.PMC10243563.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10291755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bahnisikha Barman, T Renee Dawson, Alissa M Weaver
{"title":"ER membrane contact sites: key platforms for biogenesis of RNA-containing extracellular vesicles.","authors":"Bahnisikha Barman, T Renee Dawson, Alissa M Weaver","doi":"10.1177/25152564221121444","DOIUrl":"10.1177/25152564221121444","url":null,"abstract":"<p><p>The mechanisms by which cytoplasmic cargoes such as RNAs are incorporated into extracellular vesicles (EVs) are poorly understood. In a recent article published in Developmental Cell, we describe a novel function of endoplasmic reticulum membrane contact sites (ER MCS) in regulating biogenesis of RNA-containing EVs (Barman et al., 2022). We identified the ER MCS tether protein VAP-A and the ceramide transporter CERT as key drivers of this process. VAP-A depletion and overexpression produced corresponding changes in the overall number and RNA content of secreted EVs. Further sub-fractionation of small EVs from VAP-A depleted cells revealed a distinct loss in a specific subset of dense, RNA-loaded small EVs that are critical for the transfer of miR-100 to recipient cells. Cell imaging data confirmed the loss of RNA and RNA binding proteins (RBPs) in VAP-A-knockdown multivesicular bodies. Lipid analysis of VAP-A-knockdown EVs revealed decreases in ceramides, which are known to affect EV biogenesis. Depletion of the ceramide transfer protein CERT, which interacts with its binding partner VAP-A at ER MCS, leads to similar defects in EV number and RNA content as VAP-A-knockdown. These data suggest a model for ER MCS as platforms for biogenesis of a key EV population via ceramide transfer and RNA loading.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"5 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a0/7f/10.1177_25152564221121444.PMC10065479.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9760084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sorting (Nexin-13) out Novel Insights into Endolysosomal Cholesterol Export.","authors":"Albert Lu","doi":"10.1177/25152564221114513","DOIUrl":"https://doi.org/10.1177/25152564221114513","url":null,"abstract":"<p><p>Transport in and out of the endolysosomal compartment represents a key step in the regulation of cellular cholesterol homeostasis. Despite important recent advances, how LDL-derived, free cholesterol is exported from the lumen of endolysosomes to other organelles is still a matter of debate. We recently devised a CRISPR/Cas9 genome-scale strategy to uncover genes involved in the regulation of endolysosomal cholesterol homeostasis and the functionally linked phospholipid, bis(monoacylglycerol)-phosphate. This approach confirmed known genes and pathways involved in this process, and more importantly revealed previously unrecognized roles for new players, such as Sorting Nexin-13 (SNX13). Here we discuss the unexpected regulatory role of SNX13 in endolysosomal cholesterol export.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"5 ","pages":"25152564221114513"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e6/6e/10.1177_25152564221114513.PMC10243570.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10298546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}