Contact (Thousand Oaks (Ventura County, Calif.))最新文献

{"title":"DGARM/C10orf76/ARMH3 for Ceramide Transfer Zone at the Endoplasmic Reticulum-Distal Golgi Contacts.","authors":"Aya Mizuike, Kentaro Hanada","doi":"10.1177/25152564241239443","DOIUrl":"10.1177/25152564241239443","url":null,"abstract":"<p><p>Phosphatidylinositol 4-monophosphate (PtdIns(4)P) is one of the key membrane components which mark the membrane contact sites. In the mammalian Golgi complex, PtdIns(4)P is produced at various subregions via specific mechanisms for each site. Particularly, PtdIns(4)P pools generated at the distal Golgi regions are pivotal for the determination of membrane contacts between the endoplasmic reticulum (ER) and Golgi, at which inter-organelle lipid transport takes place. In this short review, we will focus on C10orf76 (or ARMH3), which we propose to rename as DGARM after a distal Golgi armadillo repeat protein, for its function in generating a PtdIns(4)P pool crucial for ER-to-distal Golgi ceramide transport. We further discuss from the viewpoint of the evolutionary conservation of DGARM.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"7 ","pages":"25152564241239443"},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10956147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186828","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":"Editorial on Special Collection in <i>Contact</i>: VPS13 and Bridge-Like Lipid Transfer Proteins: A New Mode of Intracellular Continuity.","authors":"Tim P Levine, Liz Conibear","doi":"10.1177/25152564241238538","DOIUrl":"10.1177/25152564241238538","url":null,"abstract":"","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"7 ","pages":"25152564241238538"},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140145018","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":"Nucleus-Mitochondria Contact Sites Are Associated With Asynthetic Fission in Zebrafish Skin.","authors":"Dhani Tracey-White, Matthew J Hayes","doi":"10.1177/25152564241239445","DOIUrl":"10.1177/25152564241239445","url":null,"abstract":"<p><p>Rapid increase in body surface area of growing zebrafish larvae (<i>Danio rario</i>) is partially accomplished by asynthetic fission of superficial epithelial cells (SECs) of the skin. There are two cycles of this atypical form of cell division which is unaccompanied by DNA replication; resulting in cells with a variable DNA content. Here, electron microscopy of basal epithelium cells that give rise to these SECs in zebrafish larvae shows aggregation of mitochondria around the nucleus and the formation of nucleus-mitochondria membrane contact sites. Membrane aggregates appear in the lumen of the nuclear envelope at these sites of membrane contact in some cells, suggesting lipid turnover in this vicinity. As the epithelial cells mature and stratify, the mitochondria are engulfed by extensions arising from the nuclear envelope. The mitochondrial outer membrane fragments and mitochondria fuse with the nuclear envelope and parts of the endoplasmic reticulum. Other organelles, including the Golgi apparatus, progressively localize to a central region of the cell and lose their integrity. Thus, asynthetic fission is accompanied by an atypical pattern of organelle destruction and a prelude to this is the formation of nucleus-mitochondria membrane contact sites.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"7 ","pages":"25152564241239445"},"PeriodicalIF":0.0,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10958491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208778","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":"C<i>ool-contacts</i>: Cryo-Electron Microscopy of Membrane Contact Sites and Their Components.","authors":"Cyan Ching, Julien Maufront, Aurélie di Cicco, Daniel Lévy, Manuela Dezi","doi":"10.1177/25152564241231364","DOIUrl":"10.1177/25152564241231364","url":null,"abstract":"<p><p>Electron microscopy has played a pivotal role in elucidating the ultrastructure of membrane contact sites between cellular organelles. The advent of cryo-electron microscopy has ushered in the ability to determine atomic models of constituent proteins or protein complexes within sites of membrane contact through single particle analysis. Furthermore, it enables the visualization of the three-dimensional architecture of membrane contact sites, encompassing numerous copies of proteins, whether in vitro reconstituted or directly observed in situ using cryo-electron tomography. Nevertheless, there exists a scarcity of cryo-electron microscopy studies focused on the site of membrane contact and their constitutive proteins. This review provides an overview of the contributions made by cryo-electron microscopy to our understanding of membrane contact sites, outlines the associated limitations, and explores prospects in this field.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"7 ","pages":"25152564241231364"},"PeriodicalIF":0.0,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10895918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975351","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":"OSBP is a Major Determinant of Golgi Phosphatidylinositol 4-Phosphate Homeostasis.","authors":"Colleen P Doyle, Liz Timple, Gerald R V Hammond","doi":"10.1177/25152564241232196","DOIUrl":"10.1177/25152564241232196","url":null,"abstract":"<p><p>The lipid phosphatidylinositol 4-phosphate (PI4P) plays a master regulatory role at Golgi membranes, orchestrating membrane budding, non-vesicular lipid transport and membrane organization. It follows that harmonious Golgi function requires strictly maintained PI4P homeostasis. One of the most abundant PI4P effector proteins is the oxysterol binding protein (OSBP), a lipid transfer protein that exchanges trans-Golgi PI4P for ER cholesterol. Although this protein consumes PI4P as part of its lipid anti-porter function, whether it actively contributes to Golgi PI4P homeostasis has been questioned. Here, we employed a series of acute and chronic genetic manipulations, together with orthogonal targeting of OSBP, to interrogate its control over Golgi PI4P abundance. Modulating OSBP levels at ER:Golgi membrane contact sites produces reciprocal changes in PI4P levels. Additionally, we observe that OSBP has a high capacity for PI4P turnover, even at orthogonal organelle membranes. However, despite also visiting the plasma membrane, endogenous OSBP makes no impact on PI4P levels in this compartment. We conclude that OSBP is a major determinant of Golgi PI4P homeostasis.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"7 ","pages":"25152564241232196"},"PeriodicalIF":0.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10893830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975352","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":"Supralinear Dependence of the IP₃ Receptor-to-Mitochondria Local Ca²⁺ Transfer on the Endoplasmic Reticulum Ca²⁺ Loading.","authors":"György Csordás, David Weaver, Péter Várnai, György Hajnóczky","doi":"10.1177/25152564241229273","DOIUrl":"10.1177/25152564241229273","url":null,"abstract":"<p><p>Calcium signal propagation from endoplasmic reticulum (ER) to mitochondria regulates a multitude of mitochondrial and cell functions, including oxidative ATP production and cell fate decisions. Ca²⁺ transfer is optimal at the ER-mitochondrial contacts, where inositol 1,4,5-trisphosphate (IP₃) receptors (IP3R) can locally expose the mitochondrial Ca²⁺ uniporter (mtCU) to high [Ca²⁺] nanodomains. The Ca²⁺ loading state of the ER (Ca^2 +_ER) can vary broadly in physiological and pathological scenarios, however, the correlation between Ca^2 +_ER and the local Ca²⁺ transfer is unclear. Here, we studied IP₃-induced Ca²⁺ transfer to mitochondria at different Ca^2 +_ER in intact and permeabilized RBL-2H3 cells via fluorescence measurements of cytoplasmic [Ca²⁺] ([Ca²⁺]_c) and mitochondrial matrix [Ca²⁺] ([Ca²⁺]_m). Preincubation of intact cells in high versus low extracellular [Ca²⁺] caused disproportionally greater increase in [Ca²⁺]_m than [Ca²⁺]_c responses to IP₃-mobilizing agonist. Increasing Ca^2 +_ER by small Ca²⁺ boluses in suspensions of permeabilized cells supralinearly enhanced the mitochondrial Ca²⁺ uptake from IP₃-induced Ca²⁺ release. The IP₃-induced local [Ca²⁺] spikes exposing the mitochondrial surface measured using a genetically targeted sensor appeared to linearly correlate with Ca^2 +_ER, indicating that amplification happened in the mitochondria. Indeed, overexpression of an EF-hand deficient mutant of the mtCU gatekeeper MICU1 reduced the cooperativity of mitochondrial Ca²⁺ uptake. Interestingly, the IP₃-induced [Ca²⁺]_m signal plateaued at high Ca^2 +_ER, indicating activation of a matrix Ca²⁺ binding/chelating species. Mitochondria thus seem to maintain a \"working [Ca²⁺]_m range\" via a low-affinity and high-capacity buffer species, and the ER loading steeply enhances the IP3R-linked [Ca²⁺]_m signals in this working range.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"7 ","pages":"25152564241229273"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10868505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139743109","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":"IP₃Rs and nSOCE-Tied Together at Two Ends.","authors":"Gaiti Hasan","doi":"10.1177/25152564241231092","DOIUrl":"10.1177/25152564241231092","url":null,"abstract":"<p><p>All living organisms need to respond appropriately to changes in the extracellular milieu. Cellular mechanisms that enable such responses evolved in parallel with organismal complexity and intracellular Ca²⁺ signaling is one such mechanism where extracellular signals received at the cell membrane communicate with endoplasmic reticular stores of Ca²⁺, to stimulate appropriate Ca²⁺-mediated changes in cellular physiology. The amplitude and dynamics of endoplasmic reticulum (ER)-Ca²⁺ release in response to extracellular signals determines the nature of the cellular response. An understanding of how ER-Ca²⁺ channels might regulate cellular Ca²⁺ signaling in different cell types is lacking. In a recent paper, this question has been addressed in the context of neurons ( Chakraborty et al., 2023) and the implications of these new findings are discussed here.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"7 ","pages":"25152564241231092"},"PeriodicalIF":0.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10865778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736988","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":"Orthogonal Targeting of SAC1 to Mitochondria Implicates ORP2 as a Major Player in PM PI4P Turnover.","authors":"Colleen P Doyle, Andrew Rectenwald, Liz Timple, Gerald R V Hammond","doi":"10.1177/25152564241229272","DOIUrl":"10.1177/25152564241229272","url":null,"abstract":"<p><p>Oxysterol-binding protein (OSBP)-related proteins (ORPs) 5 and 8 have been shown to deplete the lipid phosphatidylinositol 4-phosphate (PI4P) at sites of membrane contact between the endoplasmic reticulum (ER) and plasma membrane (PM). This is believed to be caused by transport of PI4P from the PM to the ER, where PI4P is degraded by an ER-localized SAC1 phosphatase. This is proposed to power the anti-port of phosphatidylserine (PS) lipids from ER to PM, up their concentration gradient. Alternatively, ORPs have been proposed to sequester PI4P, dependent on the concentration of their alternative lipid ligand. Here, we aimed to distinguish these possibilities in living cells by orthogonal targeting of PI4P transfer and degradation to PM-mitochondria contact sites. Surprisingly, we found that orthogonal targeting of SAC1 to mitochondria enhanced PM PI4P turnover independent of targeting to contact sites with the PM. This turnover could be slowed by knock-down of soluble ORP2, which also has a major impact on PM PI4P levels even without SAC1 over-expression. The data reveal a role for contact site-independent modulation of PM PI4P levels and lipid antiport.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"7 ","pages":"25152564241229272"},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10848804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704406","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":"Contact-FP: A Dimerization-Dependent Fluorescent Protein Toolkit for Visualizing Membrane Contact Site Dynamics.","authors":"Gregory E Miner, Sidney Y Smith, Wendy K Showalter, Christina M So, Joey V Ragusa, Alex E Powers, Maria Clara Zanellati, Chih-Hsuan Hsu, Michelle F Marchan, Sarah Cohen","doi":"10.1177/25152564241228911","DOIUrl":"10.1177/25152564241228911","url":null,"abstract":"<p><p>Membrane contact sites (MCSs) are sites of close apposition between two organelles used to exchange ions, lipids, and information. Cells respond to changing environmental or developmental conditions by modulating the number, extent, or duration of MCSs. Because of their small size and dynamic nature, tools to study the dynamics of MCSs in live cells have been limited. Dimerization-dependent fluorescent proteins (ddFPs) targeted to organelle membranes are an ideal tool for studying MCS dynamics because they reversibly interact to fluoresce specifically at the interface between two organelles. Here, we build on previous work using ddFPs as sensors to visualize the morphology and dynamics of MCSs. We engineered a suite of ddFPs called Contact-FP that targets ddFP monomers to lipid droplets (LDs), the endoplasmic reticulum (ER), mitochondria, peroxisomes, lysosomes, plasma membrane, caveolae, and the cytoplasm. We show that these probes correctly localize to their target organelles. Using LDs as a test case, we demonstrate that Contact-FP pairs specifically localize to the interface between two target organelles. Titration of LD-mitochondria ddFPs revealed that these sensors can be used at high concentrations to drive MCSs or can be titrated down to minimally perturb and visualize endogenous MCSs. We show that Contact-FP probes can be used to: (1) visualize LD-mitochondria MCS dynamics, (2) observe changes in LD-mitochondria MCS dynamics upon overexpression of PLIN5, a known LD-mitochondrial tether, and (3) visualize two MCSs that share one organelle simultaneously (e.g., LD-mitochondria and LD-ER MCSs). Contact-FP probes can be optimized to visualize MCSs between any pair of organelles represented in the toolkit.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"7 ","pages":"25152564241228911"},"PeriodicalIF":0.0,"publicationDate":"2024-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10846013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704405","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":"Erythroid Differentiation Dependent Interaction of VPS13A with XK at the Plasma Membrane of K562 Cells.","authors":"Chase Amos, Peng Xu, Pietro De Camilli","doi":"10.1177/25152564231215133","DOIUrl":"10.1177/25152564231215133","url":null,"abstract":"<p><p>Mutations of the bridge-like lipid transport protein VPS13A and the lipid scramblase XK result in Chorea Acanthocytosis (ChAc) and McLeod syndrome (MLS), respectively, two similar conditions involving neurodegeneration and deformed erythrocytes (acanthocytes). VPS13A binds XK, suggesting a model in which VPS13A forms a lipid transport bridge between the endoplasmic reticulum (ER) and the plasma membrane (PM), where XK resides. However, studies of VPS13A in HeLa and COS7 cells showed that this protein localizes primarily at contacts of the ER with mitochondria. Overexpression of XK in these cells redistributed VPS13A to the biosynthetic XK pool in the ER but not to PM-localized XK. Colocalization of VPS13A with XK at the PM was only observed if overexpressed XK harbored mutations that disengaged its VPS13A-binding site from an intramolecular interaction. As the acanthocytosis phenotype of ChAc and MLS suggests a role of the two proteins in cells of the erythroid lineage, we explored their localization in K562 cells, which differentiate into erythroblasts upon hemin addition. When tagged VPS13A was overexpressed in hemin-treated K562 cells, robust formation of ER-PM contacts positive for VPS13A was observed and their formation was abolished in XK KO cells. ER-PM contacts positive for VPS13A were seldom observed in undifferentiated K562 cells, despite the presence of XK in these cells at concentrations similar to those observed after differentiation. These findings reveal that the interaction of VPS13A with XK at ER-PM contacts requires a permissive state which depends upon cell type and/or functional state of the cell.</p>","PeriodicalId":101304,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"6 ","pages":"25152564231215133"},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10748539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139033150","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}