A dual role of ERGIC-localized Rabs in TMED10-mediated unconventional protein secretion

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(7), P. 1077 - 1092

Published: June 26, 2024

Language: Английский

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Any1 is a phospholipid scramblase involved in endosome biogenesis

The Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 224(4)

Published: March 6, 2025

Endosomes are central organelles in the recycling and degradation of receptors membrane proteins. Once endocytosed, such proteins sorted at endosomes into intraluminal vesicles (ILVs). The resulting multivesicular bodies (MVBs) then fuse with lysosomes, leading to ILVs monomers. However, biogenesis MVBs requires a constant lipid supply for efficient ILV formation. An ER-endosome contact site has been suggested play critical role MVB biogenesis. Here, we identify Any1 as novel phospholipid scramblase, which functions transfer protein Vps13 We uncover that cycles between early Golgi colocalizes Vps13, possibly here-discovered potential droplets (LDs) endosomes. Strikingly, both required formation, presumably couple flux homeostasis during formation endosome maturation.

Language: Английский

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Lipophagy at a glance

Journal of Cell Science, Journal Year: 2022, Volume and Issue: 135(5)

Published: March 1, 2022

Lipophagy is a central cellular process for providing the cell with readily utilized, high energy source of neutral lipids. Since its discovery over decade ago, we are just starting to understand molecular components that drive lipophagy, how it activated in response nutrient availability, and potential as therapeutic target disease. In this Cell Science at Glance article accompanying poster, first provide brief overview different structural enzymatic proteins comprise lipid droplet (LD) proteome reside within limiting phospholipid monolayer complex organelle. We then highlight key players catabolic breakdown LDs during functionally linked lipolysis lipophagy processes. Finally, discuss what currently known about macro- micro-lipophagy based on findings yeast, mammalian other model systems, impairment these important functions can lead disease states.

Language: Английский

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The Golgi Apparatus and its Next-Door Neighbors

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: April 28, 2022

The Golgi apparatus represents a central compartment of membrane traffic. Its apparent architecture, however, differs considerably among species, from unstacked and scattered cisternae in the budding yeast Saccharomyces cerevisiae to beautiful ministacks plants further gigantic ribbon structures typically seen mammals. Considering well-conserved functions Golgi, its fundamental structure must have been optimized despite seemingly different architectures. In addition core layers cisternae, is usually accompanied by next-door compartments on cis trans sides. -Golgi network (TGN) can be now considered as independent stack. On side, intermediate between ER (ERGIC) has known mammalian cells, functional equivalent suggested for plant cells. High-resolution live imaging extremely powerful elucidating dynamics these revealed amazing similarities their behaviors, indicating common mechanisms conserved along long course evolution. From new findings, I would like propose reconsideration suggest concept describe roles comprehensively around post-Golgi trafficking.

Language: Английский

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Regulatory sites in the Mon1–Ccz1 complex control Rab5 to Rab7 transition and endosome maturation

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(30)

Published: July 18, 2023

Maturation from early to late endosomes depends on the exchange of their marker proteins Rab5 Rab7. This requires Rab7 activation by its specific guanine nucleotide factor (GEF) Mon1–Ccz1. Efficient GEF activity this complex membranes Rab5, thus driving Rab–GTPase endosomes. However, molecular details role in Mon1–Ccz1 are unclear. Here, we identify key features Mon1 involved regulation. We show that intrinsically disordered N-terminal domain autoinhibits Rab5-dependent membranes. Consequently, truncations result higher vitro and alterations endosomal structures Drosophila nephrocytes. A shift more Rab7-positive yeast suggests faster maturation. Using modeling, further a conserved Rab5-binding site Mon1. Mutations impairing interaction poor growth defects vivo. Our analysis provides framework understand mechanism Ras-related brain (Rab) conversion organelle maturation along endomembrane system.

Language: Английский

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Rab7/Retromer‐based endolysosomal trafficking is essential for proper host invasion in rice blast

New Phytologist, Journal Year: 2023, Volume and Issue: 239(4), P. 1384 - 1403

Published: June 9, 2023

Summary Secretion is a fundamental process that plant pathogens utilize to deliver effectors into the host downregulate immunity and promote infection. Here, we uncover fascinating membrane trafficking delivery route originates from vacuolar membranes in Magnaporthe oryzae conduits interface plasma membrane. To perform such secretory/trafficking function, MoRab7 first recruits retromer complex membrane, enabling recognition of family SNARE proteins, including MoSnc1. Live‐cell imaging confirmed highly dynamic vesicular component(s) MoSnc1 toward across or subsequent fusion with target membranes. Interestingly, disruption MoRab7/Retromer/MoSnc1‐based endolysosomal cascade affects effector secretion fungal pathogenicity. Taken together, discovered an unconventional protein starting endolysosomes M. –rice interaction dissect role MoRab7/Retromer/MoSnc1 sorting machinery during biotrophy invasive growth rice blast fungus.

Language: Английский

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Structural organization of the retriever–CCC endosomal recycling complex

Nature Structural & Molecular Biology, Journal Year: 2023, Volume and Issue: 31(6), P. 910 - 924

Published: Dec. 7, 2023

Language: Английский

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Cryo-EM structure of the Mon1–Ccz1–RMC1 complex reveals molecular basis of metazoan RAB7A activation

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(22)

Published: May 22, 2023

Understanding of the evolution metazoans from their unicellular ancestors is a fundamental question in biology. In contrast to fungi which utilize Mon1–Ccz1 dimeric complex activate small GTPase RAB7A, rely on Mon1–Ccz1–RMC1 trimeric complex. Here, we report near-atomic resolution cryogenic-electron microscopy structure Drosophila RMC1 acts as scaffolding subunit and binds both Mon1 Ccz1 surface opposite RAB7A-binding site, with many RMC1-contacting residues unique metazoans, explaining binding specificity. Significantly, assembly required for cellular RAB7A activation, autophagic functions organismal development zebrafish. Our studies offer molecular explanation different degree conservation across species, provide an excellent example how metazoan-specific proteins take over existing organisms.

Language: Английский

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Insights into the role of the membranes in Rab GTPase regulation

Current Opinion in Cell Biology, Journal Year: 2023, Volume and Issue: 83, P. 102177 - 102177

Published: June 15, 2023

Rab GTPases are molecular switches with essential roles in mediating vesicular trafficking and establishing organelle identity. The conversion from the inactive, cytosolic to membrane-bound, active species back is tightly controlled by regulatory proteins. Recently, of membrane properties lipid composition different target organelles determining activity state Rabs have come light. investigation several guanine nucleotide exchange factors (GEFs) has revealed principles how recruitment via interactions spatial confinement on surface contribute spatiotemporal specificity GTPase network. This paints an intricate picture control mechanisms activation highlights importance code organization endomembrane system.

Language: Английский

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Structure of the endosomal CORVET tethering complex

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 19, 2024

Abstract Cells depend on their endolysosomal system for nutrient uptake and downregulation of plasma membrane proteins. These processes rely endosomal maturation, which requires multiple fusion steps. Early endosome is promoted by the Rab5 GTPase its effector, hexameric CORVET tethering complex, homologous to lysosomal HOPS. How these related complexes recognize specific target membranes remains entirely elusive. Here, we solve structure cryo-electron microscopy revealed minimal requirements tethering. As expected, core HOPS resembles each other. However, function-defining subunits show marked structural differences. Notably, discover that unlike HOPS, depends not only but also phosphatidylinositol-3-phosphate (PI3P) lipid packing defects tethering, implying an organelle-specific code enables fusion. Our data suggest both shape interactions are conserved in metazoans, thus providing a paradigm how function.

Language: Английский

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