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

{"title":"Get Closer to the World of Contact Sites: A Beginner's Guide to Proximity-Driven Fluorescent Probes.","authors":"Elena Poggio,&nbsp;Marisa Brini,&nbsp;Tito Calì","doi":"10.1177/25152564221135748","DOIUrl":"https://doi.org/10.1177/25152564221135748","url":null,"abstract":"<p><p>To maintain cellular homeostasis and to coordinate the proper response to a specific stimulus, information must be integrated throughout the cell in a well-organized network, in which organelles are the crucial nodes and membrane contact sites are the main edges. Membrane contact sites are the cellular subdomains where two or more organelles come into close apposition and interact with each other. Even though many inter-organelle contacts have been identified, most of them are still not fully characterized, therefore their study is an appealing and expanding field of research. Thanks to significant technological progress, many tools are now available or are in rapid development, making it difficult to choose which one is the most suitable for answering a specific biological question. Here we distinguish two different experimental approaches for studying inter-organelle contact sites. The first one aims to morphologically characterize the sites of membrane contact and to identify the molecular players involved, relying mainly on the application of biochemical and electron microscopy (EM)-related methods. The second approach aims to understand the functional importance of a specific contact, focusing on spatio-temporal details. For this purpose, proximity-driven fluorescent probes are the experimental tools of choice, since they allow the monitoring and quantification of membrane contact sites and their dynamics in living cells under different cellular conditions or upon different stimuli. In this review, we focus on these tools with the purpose of highlighting their great versatility and how they can be applied in the study of membrane contacts. We will extensively describe all the different types of proximity-driven fluorescent tools, discussing their benefits and drawbacks, ultimately providing some suggestions to choose and apply the appropriate methods on a case-to-case basis and to obtain the best experimental outcomes.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"5 ","pages":"25152564221135748"},"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/4a/fd/10.1177_25152564221135748.PMC10243574.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10077032","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":"Regulation of Endosomal Sorting and Maturation by ER-Endosome Contact Sites.","authors":"Steve Jean,&nbsp;Sonya Nassari","doi":"10.1177/25152564221106046","DOIUrl":"https://doi.org/10.1177/25152564221106046","url":null,"abstract":"<p><p>Endosomes are a heterogeneous population of intracellular organelles responsible for sorting, recycling, or transporting internalized materials for degradation. Endosomal sorting and maturation are controlled by a complex interplay of regulators, with RAB GTPases and phosphoinositides playing key roles. In this decade, another layer of regulation surfaced with the role played by membrane contact sites between the endoplasmic reticulum (ER) and endosomes. Specific regulators of ER-endosome contact sites or proteins localized at these sites are emerging as modulators of this complex endosomal ballet. In particular, lipid transfer or recruitment of various complexes and enzymes at ER-endosome contact sites play an active role in endosome sorting, scission, and maturation. In this short review, we focus on studies describing ER-endosome contact sites in these three endosomal processes.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"5 ","pages":"25152564221106046"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10298543","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":"Molecular Regulations of FUNDC1 at ER-Mitochondria Contacts Under Hypoxic Stress.","authors":"Yi Zhang,&nbsp;Haixia Zhuang,&nbsp;Hao Liu,&nbsp;Du Feng","doi":"10.1177/25152564221092487","DOIUrl":"https://doi.org/10.1177/25152564221092487","url":null,"abstract":"<p><p>A recent research paper published in Journal of Cell Biology by Chen and colleagues describes a novel mechanism by which the MAM (Mitochondrial-associated endoplasmic reticulum membrane) protein FUNDC1 (FUN14 domain-containing protein 1) regulates mitochondrial division through altered protein post-translational modifications under hypoxic stress. The authors found that in a hypoxic environment, the endoplasmic reticulum-localized deubiquitinating enzyme USP19 accumulates at the MAM and interacts with the enriched mitochondrial outer membrane protein FUNDC1, which subsequently induces its deubiquitination and promotes the oligomerization and activity of DRP1, and mitochondria eventually divide in the presence of DRP1. This article provides new insights into the regulation of mitochondrial dynamics by FUNDC1 under hypoxic condition.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"5 ","pages":"25152564221092487"},"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/08/9c/10.1177_25152564221092487.PMC10243562.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10291754","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":"Inositol triphosphate signaling triggers lysosome biogenesis via calcium release from endoplasmic reticulum stores.","authors":"Mouhannad Malek,&nbsp;Volker Haucke","doi":"10.1177/25152564221097052","DOIUrl":"https://doi.org/10.1177/25152564221097052","url":null,"abstract":"<p><p>Lysosomes serve as cellular degradation and signaling centers that coordinate the turnover of macromolecules with cell metabolism. The adaptation of cellular lysosome content and activity via the induction of lysosome biogenesis is therefore key to cell physiology and to counteract disease. Previous work has established a pathway for the induction of lysosome biogenesis in signaling-inactive starved cells that is based on the repression of mTORC1-mediated nutrient signaling. How lysosomal biogenesis is facilitated in signaling-active fed cells is poorly understood. A recent study by Malek et al (Malek <i>et al</i>, 2022) partially fills this gap by unraveling a nutrient signaling-independent pathway for lysosome biogenesis that operates in signaling-active cells. This pathway involves the receptor-mediated activation of phospholipase C, inositol (1,4,5)-triphosphate (IP₃)-triggered release of calcium ions from endoplasmic reticulum stores, and the calcineurin-induced activation of transcription factor EB (TFEB) and its relative TFE3 to induce lysosomal gene expression independent of calcium in the lysosome lumen. These findings contribute to our understanding of how lysosome biogenesis and function are controlled in response to environmental changes and cell signaling and may conceivably be of relevance for our understanding and the treatment of lysosome-related diseases as well as for aging and neurodegeneration.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":" ","pages":"251525642210970"},"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/44/d3/10.1177_25152564221097052.PMC7612895.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40402643","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":"α-Synuclein Interactions in Mitochondria-ER Contacts: A Possible Role in Parkinson's Disease.","authors":"Adolfo Garcia Erustes,&nbsp;Gabriel Cicolin Guarache,&nbsp;Erika da Cruz Guedes,&nbsp;Anderson Henrique França Figueredo Leão,&nbsp;Gustavo José da Silva Pereira,&nbsp;Soraya Soubhi Smaili","doi":"10.1177/25152564221119347","DOIUrl":"https://doi.org/10.1177/25152564221119347","url":null,"abstract":"<p><p>Endoplasmic reticulum-mitochondria contact sites regulate various biological processes, such as mitochondrial dynamics, calcium homeostasis, autophagy and lipid metabolism. Notably, dysfunctions in these contact sites are closely related to neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. However, details about the role of endoplasmic reticulum-mitochondria contact sites in neurodegenerative diseases remain unknown. In Parkinson's disease, interactions between α-synuclein in the contact sites and components of tether complexes that connect organelles can lead to various dysfunctions, especially with regards to calcium homeostasis. This review will summarize the main tether complexes present in endoplasmic reticulum-mitochondria contact sites, and their roles in calcium homeostasis and trafficking. We will discuss the impact of α-synuclein accumulation, its interaction with tethering complex components and the implications in Parkinson's disease pathology.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"5 ","pages":"25152564221119347"},"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/b4/9a/10.1177_25152564221119347.PMC10243560.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10291749","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":"Autophagy of the ER requires actin assembly driven by the interaction of ER with endocytic pits.","authors":"Peter Novick,&nbsp;Dongmei Liu,&nbsp;Susan Ferro-Novick","doi":"10.1177/25152564221093215","DOIUrl":"10.1177/25152564221093215","url":null,"abstract":"<p><p>Autophagy of the cortical ER in budding yeast was unexpectedly found to require End3, a component of the endocytic machinery that promotes the assembly of actin at endocytic pits on the plasma membrane. The cortical ER transiently interacts with invaginating endocytic pits through a linkage consisting of VAP proteins, oxysterol binding proteins and type I myosins. These proteins are required for actin assembly and for autophagy of the ER. Assembly of actin at these contact sites may direct the movement of ER away from the cortex towards sites of autophagosome assembly.</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/75/27/10.1177_25152564221093215.PMC10129067.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9704231","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":"Vps13 is required for efficient autophagy in <i>Saccharomyces cerevisiae</i>.","authors":"Yuchen Lei,&nbsp;Xin Wen,&nbsp;Daniel J Klionsky","doi":"10.1177/25152564221136388","DOIUrl":"10.1177/25152564221136388","url":null,"abstract":"<p><p>Vps13 is a large, conserved protein that transports lipids between membranes. Its localization at multiple organelle membranes and membrane contact sites suggests its important physiological roles. In addition, the high correlation of mutant <i>VPS13</i> with certain diseases, especially those involving neurodegeneration, makes this protein of considerable biomedical interest. Taking advantage of the fact that yeasts only have one Vps13 protein, the roles of yeast Vps13 have been well studied. However, whether and how Vps13 functions in macroautophagy/autophagy, a process of degradation of cytoplasmic cargoes, have been elusive questions. In this paper, we investigated the role of Vps13 in both non-selective and selective autophagy and found that this protein participates in non-selective autophagy, reticulophagy and pexophagy, but not mitophagy, and that Vps13 plays a role in the late stage of autophagy.</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/65/9e/10.1177_25152564221136388.PMC10162780.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9443153","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":"Ca²⁺ Signalling is a Conserved Game of Contact.","authors":"Hannah Casbolt,&nbsp;Michelangelo Campanella","doi":"10.1177/25152564221095961","DOIUrl":"https://doi.org/10.1177/25152564221095961","url":null,"abstract":"<p><p>Apicoplasts are critical for the growth of medically important parasites. It is now reported that they form contacts with the endoplasmic reticulum (ER) via two pore channels thus enabling Ca²⁺ trafficking. This highlights the dynamic physical association between organelles as a critical motif in Ca²⁺ signaling.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"5 ","pages":"25152564221095961"},"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/f4/f1/10.1177_25152564221095961.PMC10243581.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10291753","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":"Sequence Analysis and Structural Predictions of Lipid Transfer Bridges in the Repeating Beta Groove (RBG) Superfamily Reveal Past and Present Domain Variations Affecting Form, Function and Interactions of VPS13, ATG2, SHIP164, Hobbit and Tweek.","authors":"Tim P Levine","doi":"10.1177/25152564221134328","DOIUrl":"https://doi.org/10.1177/25152564221134328","url":null,"abstract":"<p><p>Lipid transfer between organelles requires proteins that shield the hydrophobic portions of lipids as they cross the cytoplasm. In the last decade a new structural form of lipid transfer protein (LTP) has been found: long hydrophobic grooves made of beta-sheet that bridge between organelles at membrane contact sites. Eukaryotes have five families of bridge-like LTPs: VPS13, ATG2, SHIP164, Hobbit and Tweek. These are unified into a single superfamily through their bridges being composed of just one domain, called the repeating beta groove (RBG) domain, which builds into rod shaped multimers with a hydrophobic-lined groove and hydrophilic exterior. Here, sequences and predicted structures of the RBG superfamily were analyzed in depth. Phylogenetics showed that the last eukaryotic common ancestor contained all five RBG proteins, with duplicated VPS13s. The current set of long RBG protein appears to have arisen in even earlier ancestors from shorter forms with 4 RBG domains. The extreme ends of most RBG proteins have amphipathic helices that might be an adaptation for direct or indirect bilayer interaction, although this has yet to be tested. The one exception to this is the C-terminus of SHIP164, which instead has a coiled-coil. Finally, the exterior surfaces of the RBG bridges are shown to have conserved residues along most of their length, indicating sites for partner interactions almost all of which are unknown. These findings can inform future cell biological and biochemical experiments.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"5 ","pages":"251525642211343"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10438231","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":"Quantitative Models of Lipid Transfer and Membrane Contact Formation.","authors":"Yongli Zhang,&nbsp;Jinghua Ge,&nbsp;Xin Bian,&nbsp;Avinash Kumar","doi":"10.1177/25152564221096024","DOIUrl":"https://doi.org/10.1177/25152564221096024","url":null,"abstract":"<p><p>Lipid transfer proteins (LTPs) transfer lipids between different organelles, and thus play key roles in lipid homeostasis and organelle dynamics. The lipid transfer often occurs at the membrane contact sites (MCS) where two membranes are held within 10-30 nm. While most LTPs act as a shuttle to transfer lipids, recent experiments reveal a new category of eukaryotic LTPs that may serve as a bridge to transport lipids in bulk at MCSs. However, the molecular mechanisms underlying lipid transfer and MCS formation are not well understood. Here, we first review two recent studies of extended synaptotagmin (E-Syt)-mediated membrane binding and lipid transfer using novel approaches. Then we describe mathematical models to quantify the kinetics of lipid transfer by shuttle LTPs based on a lipid exchange mechanism. We find that simple lipid mixing among membranes of similar composition and/or lipid partitioning among membranes of distinct composition can explain lipid transfer against a concentration gradient widely observed for LTPs. We predict that selective transport of lipids, but not membrane proteins, by bridge LTPs leads to osmotic membrane tension by analogy to the osmotic pressure across a semipermeable membrane. A gradient of such tension and the conventional membrane tension may drive bulk lipid flow through bridge LTPs at a speed consistent with the fast membrane expansion observed <i>in vivo</i>. Finally, we discuss the implications of membrane tension and lipid transfer in organelle biogenesis. Overall, the quantitative models may help clarify the mechanisms of LTP-mediated MCS formation and lipid transfer.</p>","PeriodicalId":10556,"journal":{"name":"Contact (Thousand Oaks (Ventura County, Calif.))","volume":"5 ","pages":"1-21"},"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/60/c5/10.1177_25152564221096024.PMC9481209.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10079411","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}