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Contact (CTC)
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This is an Open Access Journal

Open Access journal
ISSN (Online) 2515-2564
Published by Sage Publications

[1174 journals]

Regulation of Endosomal Sorting and Maturation by ER-Endosome Contact
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- Authors: Steve Jean, Sonya Nassari
  Abstract: Contact, Volume 5, Issue , January-December 2022.
  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.
  Citation: Contact
  PubDate: 2022-06-09T01:18:03Z
  DOI: 10.1177/25152564221106046
  Issue No: Vol. 5 (2022)
The PH-like Domain of VPS13 Proteins - a Determinant of Localization to
the Golgi Apparatus or to the Plasma Membrane
- Authors: Joanna Kaminska
  Abstract: Contact, Volume 5, Issue , January-December 2022.
  Mutations in the four human genes VPS13A-D, 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.
  Citation: Contact
  PubDate: 2022-06-09T01:17:41Z
  DOI: 10.1177/25152564221106024
  Issue No: Vol. 5 (2022)
Ca2+ Signalling is a Conserved Game of Contact
- Authors: Hannah Casbolt, Michelangelo Campanella
  Abstract: Contact, Volume 5, Issue , January-December 2022.
  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.
  Citation: Contact
  PubDate: 2022-06-09T01:17:24Z
  DOI: 10.1177/25152564221095961
  Issue No: Vol. 5 (2022)
Inositol Triphosphate Signaling Triggers Lysosome Biogenesis Via Calcium
Release from Endoplasmic Reticulum Stores
- Authors: Mouhannad Malek, Volker Haucke
  Abstract: Contact, Volume 5, Issue , January-December 2022.
  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. (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.
  Citation: Contact
  PubDate: 2022-06-01T05:39:08Z
  DOI: 10.1177/25152564221097052
  Issue No: Vol. 5 (2022)
Moving Lipids, by the Numbers
- Authors: Pascal F. Egea
  Abstract: Contact, Volume 5, Issue , January-December 2022.
  
  Citation: Contact
  PubDate: 2022-05-30T06:13:31Z
  DOI: 10.1177/25152564221103080
  Issue No: Vol. 5 (2022)
Multiple Ways to Keep FFAT Under Control!
- Authors: Suzan Kors, Michael Schrader, Joseph L. Costello
  Abstract: Contact, Volume 5, Issue , January-December 2022.
  Peroxisomes and the ER are closely inter-connected organelles, which collaborate in the metabolism of lipids. In a recent research paper in the Journal of Cell Biology, we describe a novel mechanism by which peroxisome-ER membrane contact sites are regulated, via phosphorylation of the peroxisomal protein ACBD5. We found that the interaction between ACBD5 and the ER protein VAPB, which we have previously shown to form a tether complex at peroxisome-ER contacts, is controlled by phosphorylation of ACBD5 at two different sites of its FFAT motif – the VAPB binding site. We also identify the kinase GSK3-β as being responsible for direct phosphorylation of ACBD5 to negatively regulate interaction with VAPB, leading to reduced peroxisome-ER contacts. In this article we provide additional insights into how this work, in combination with other studies on phosphorylation of VAP interactors, suggests a complex system of both positive and negative regulation of the FFAT motif via phosphorylation.
  Citation: Contact
  PubDate: 2022-05-11T07:20:42Z
  DOI: 10.1177/25152564221101219
  Issue No: Vol. 5 (2022)
Quantitative Models of Lipid Transfer and Membrane Contact Formation
- Authors: Yongli Zhang, Jinghua Ge, Xin Bian, Avinash Kumar
  Abstract: Contact, Volume 5, Issue , January-December 2022.
  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 in vivo. 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.
  Citation: Contact
  PubDate: 2022-05-05T05:12:35Z
  DOI: 10.1177/25152564221096024
  Issue No: Vol. 5 (2022)
Nuclear Interactions: A Spotlight on Nuclear Mitochondrial Membrane
Contact Sites
- Authors: Jana Ovciarikova, Shikha Shikha, Lilach Sheiner
  Abstract: Contact, Volume 5, Issue , January-December 2022.
  Membrane contact sites (MCS) are critical for cellular functions of eukaryotes, as they enable communication and exchange between organelles. Research over the last decade unravelled the function and composition of MCS between a variety of organelles including mitochondria, ER, plasma membrane, lysosomes, lipid droplets, peroxisome and endosome, to name a few. In fact, MCS are found between any pair of organelles studied to date, with common functions including lipid exchange, calcium signalling and organelle positioning in the cell. Work in the past year has started addressing the composition and function of nuclear-mitochondrial MCS. Tether components mediating these contacts in yeast have been identified via comprehensive phenotypic screens, which also revealed a possible link between this contact and phosphatidylcholine metabolism. In human cells, and in the protozoan parasites causing malaria, proximity between these organelles is proposed to promote cell survival via a mitochondrial retrograde response. These pioneering studies should inspire the field to explore what cellular processes depend on the exchange between the nucleus and the mitochondrion, given that they play such central roles in cell biology.
  Citation: Contact
  PubDate: 2022-05-03T11:19:52Z
  DOI: 10.1177/25152564221096217
  Issue No: Vol. 5 (2022)
Autophagy of the ER Requires Actin Assembly Driven by the Interaction of
ER with Endocytic Pits
- Authors: Peter Novick, Dongmei Liu, Susan Ferro-Novick
  Abstract: Contact, Volume 5, Issue , January-December 2022.
  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.
  Citation: Contact
  PubDate: 2022-04-13T07:02:56Z
  DOI: 10.1177/25152564221093215
  Issue No: Vol. 5 (2022)
Molecular Regulations of FUNDC1 at ER-Mitochondria Contacts Under Hypoxic
Stress
- Authors: Yi Zhang, Haixia Zhuang, Hao Liu, Du Feng
  Abstract: Contact, Volume 5, Issue , January-December 2022.
  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.
  Citation: Contact
  PubDate: 2022-04-06T05:58:44Z
  DOI: 10.1177/25152564221092487
  Issue No: Vol. 5 (2022)