Faculty Opinions recommendation of A novel, retromer-independent role for sorting nexins 1 and 2 in RhoG-dependent membrane remodeling.

The sorting nexins (SNX), constitute a diverse family of molecules that play varied roles in membrane trafficking, cell signaling, membrane remodeling, organelle motility and autophagy. In particular, the SNX-BAR proteins, a SNX subfamily characterized by a C-terminal dimeric Bin/Amphiphysin/Rvs (BAR) lipid curvature domain and a conserved Phox-homology domain, are of great interest. In budding yeast, many SNX-BARs proteins have well-characterized endo-vacuolar trafficking roles. Phylogenetic analyses allowed us to identify an additional SNX-BAR protein, Vps501, with a novel endo-vacuolar role. We report that Vps501 uniquely localizes to the vacuolar membrane and works with the SEA complex to regulate autophagy. Furthermore, we found cells displayed a severe deficiency in starvation-induced/nonselective autophagy only when SEA complex subunits are ablated in combination with Vps501, indicating a cooperative role with the SEA complex during autophagy. Additionally, we found the SEA complex becomes destabilized in vps501Δsea1Δ cells, which resulted in aberrant TORC1 hyperactivity and misregulation of autophagy induction.

Download Full-text

Correlative AFM and fluorescence imaging demonstrate nanoscale membrane remodeling and ring-like and tubular structure formation by septins

Nanoscale ◽

10.1039/d1nr01978c ◽

2021 ◽

Author(s):

Anthony Vial ◽

Cyntia Taveneau ◽

Luca Costa ◽

brieuc chauvin ◽

hussein nasrallah ◽

...

Keyword(s):

Plasma Membrane ◽

Cell Division ◽

Structure Formation ◽

Fluorescence Imaging ◽

Tubular Structure ◽

Membrane Remodeling

Septins are ubiquitous cytoskeletal filaments that interact with the inner plasma membrane and are essential for cell division in eukaryotes. In cellular contexts, septins are often localized at micrometric gaussian...

Download Full-text

The role of VPS4 in ESCRT-III polymer remodeling

Biochemical Society Transactions ◽

10.1042/bst20180026 ◽

2019 ◽

Vol 47 (1) ◽

pp. 441-448 ◽

Cited By ~ 8

Author(s):

Christophe Caillat ◽

Sourav Maity ◽

Nolwenn Miguet ◽

Wouter H. Roos ◽

Winfried Weissenhorn

Keyword(s):

Active Role ◽

Mechanistic Models ◽

Membrane Remodeling ◽

Filament Formation ◽

Enveloped Viruses ◽

Endosomal Sorting ◽

Membrane Fission ◽

Dynamic Assembly ◽

Inside Out

Abstract The endosomal sorting complex required for transport-III (ESCRT-III) and VPS4 catalyze a variety of membrane-remodeling processes in eukaryotes and archaea. Common to these processes is the dynamic recruitment of ESCRT-III proteins from the cytosol to the inner face of a membrane neck structure, their activation and filament formation inside or at the membrane neck and the subsequent or concomitant recruitment of the AAA-type ATPase VPS4. The dynamic assembly of ESCRT-III filaments and VPS4 on cellular membranes induces constriction of membrane necks with large diameters such as the cytokinetic midbody and necks with small diameters such as those of intraluminal vesicles or enveloped viruses. The two processes seem to use different sets of ESCRT-III filaments. Constriction is then thought to set the stage for membrane fission. Here, we review recent progress in understanding the structural transitions of ESCRT-III proteins required for filament formation, the functional role of VPS4 in dynamic ESCRT-III assembly and its active role in filament constriction. The recent data will be discussed in the context of different mechanistic models for inside-out membrane fission.

Download Full-text

SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways

The Journal of Cell Biology ◽

10.1083/jcb.201111121 ◽

2012 ◽

Vol 197 (2) ◽

pp. 219-230 ◽

Cited By ~ 114

Author(s):

Florian Steinberg ◽

Kate J. Heesom ◽

Mark D. Bass ◽

Peter J. Cullen

Keyword(s):

Isotope Labeling ◽

Degradation Pathway ◽

Lysosomal Degradation ◽

Sorting Nexins ◽

Retromer Complex ◽

Proteomic Approach ◽

Cytoplasmic Tails ◽

Npxy Motif ◽

Global Identification ◽

Insight Into

The FERM-like domain–containing sorting nexins of the SNX17/SNX27/SNX31 family have been proposed to mediate retrieval of transmembrane proteins from the lysosomal pathway. In this paper, we describe a stable isotope labeling with amino acids in culture–based quantitative proteomic approach that allows an unbiased, global identification of transmembrane cargoes that are rescued from lysosomal degradation by SNX17. This screen revealed that several integrins required SNX17 for their stability, as depletion of SNX17 led to a loss of β1 and β5 integrins and associated a subunits from HeLa cells as a result of increased lysosomal degradation. SNX17 bound to the membrane distal NPXY motif in β integrin cytoplasmic tails, thereby preventing lysosomal degradation of β integrins and their associated a subunits. Furthermore, SNX17-dependent retrieval of integrins did not depend on the retromer complex. Consistent with an effect on integrin recycling, depletion of SNX17 also caused alterations in cell migration. Our data provide mechanistic insight into the retrieval of internalized integrins from the lysosomal degradation pathway, a prerequisite for subsequent recycling of these matrix receptors.

Download Full-text

The DHR1 Domain of DOCK180 Binds to SNX5 and Regulates Cation-independent Mannose 6-phosphate Receptor Transport

Molecular Biology of the Cell ◽

10.1091/mbc.e08-03-0314 ◽

2008 ◽

Vol 19 (9) ◽

pp. 3823-3835 ◽

Cited By ~ 18

Author(s):

Shigeo Hara ◽

Etsuko Kiyokawa ◽

Shun-ichiro Iemura ◽

Tohru Natsume ◽

Thomas Wassmer ◽

...

Keyword(s):

Guanine Nucleotide Exchange Factor ◽

Retrograde Transport ◽

Small Gtpases ◽

Guanine Nucleotide ◽

Nucleotide Exchange ◽

Sorting Nexins ◽

Exchange Factor ◽

Guanine Nucleotide Exchange ◽

Nucleotide Exchange Factor ◽

Mannose 6 Phosphate

DOCK180 is the archetype of the DOCK180-family guanine nucleotide exchange factor for small GTPases Rac1 and Cdc42. DOCK180-family proteins share two conserved domains, called DOCK homology region (DHR)-1 and -2. Although the function of DHR2 is to activate Rac1, DHR1 is required for binding to phosphoinositides. To better understand the function of DHR1, we searched for its binding partners by direct nanoflow liquid chromatography/tandem mass spectrometry, and we identified sorting nexins (SNX) 1, 2, 5, and 6, which make up a multimeric protein complex mediating endosome-to-trans-Golgi-network (TGN) retrograde transport of the cation-independent mannose 6-phosphate receptor (CI-MPR). Among these SNX proteins, SNX5 was coimmunoprecipitated with DOCK180 most efficiently. In agreement with this observation, DOCK180 colocalized with SNX5 at endosomes. The RNA interference-mediated knockdowns of SNX5 and DOCK180, but not Rac1, resulted in the redistribution of CI-MPR from TGN to endosomes. Furthermore, expression of the DOCK180 DHR1 domain was sufficient to restore the perturbed CI-MPR distribution in DOCK180 knockdown cells. These data suggest that DOCK180 regulates CI-MPR trafficking via SNX5 and that this function is independent of its guanine nucleotide exchange factor activity toward Rac1.

Download Full-text

Membrane Remodeling as a Key Player of the Hepatotoxicity Induced by Co-Exposure to Benzo[a]pyrene and Ethanol of Obese Zebrafish Larvae

Biomolecules ◽

10.3390/biom8020026 ◽

2018 ◽

Vol 8 (2) ◽

pp. 26 ◽

Cited By ~ 3

Author(s):

Muhammad Imran ◽

Odile Sergent ◽

Arnaud Tête ◽

Isabelle Gallais ◽

Martine Chevanne ◽

...

Keyword(s):

Membrane Remodeling ◽

Zebrafish Larvae

Download Full-text

Membrane Remodeling by the Double-Barrel Scaffolding Protein of Poxvirus

PLoS Pathogens ◽

10.1371/journal.ppat.1002239 ◽

2011 ◽

Vol 7 (9) ◽

pp. e1002239 ◽

Cited By ~ 31

Author(s):

Jae-Kyung Hyun ◽

Cathy Accurso ◽

Marcel Hijnen ◽

Philipp Schult ◽

Anne Pettikiriarachchi ◽

...

Keyword(s):

Scaffolding Protein ◽

Membrane Remodeling

Download Full-text

All ways lead to Rome: assembly of retromer on membranes with different sorting nexins

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00561-z ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Xin Yong ◽

Daniel D. Billadeau ◽

Da Jia

Keyword(s):

Sorting Nexins

Download Full-text

FAM92A1 is a BAR domain protein required for mitochondrial ultrastructure and function

The Journal of Cell Biology ◽

10.1083/jcb.201806191 ◽

2018 ◽

Vol 218 (1) ◽

pp. 97-111 ◽

Cited By ~ 7

Author(s):

Liang Wang ◽

Ziyi Yan ◽

Helena Vihinen ◽

Ove Eriksson ◽

Weihuan Wang ◽

...

Keyword(s):

Mitochondrial Function ◽

Molecular Mechanisms ◽

Membrane Curvature ◽

Mitochondrial Morphology ◽

Membrane Remodeling ◽

Mitochondrial Ultrastructure ◽

Bar Domain ◽

Bar Domain Proteins ◽

Domain Protein

Mitochondrial function is closely linked to its dynamic membrane ultrastructure. The mitochondrial inner membrane (MIM) can form extensive membrane invaginations known as cristae, which contain the respiratory chain and ATP synthase for oxidative phosphorylation. The molecular mechanisms regulating mitochondrial ultrastructure remain poorly understood. The Bin-Amphiphysin-Rvs (BAR) domain proteins are central regulators of diverse cellular processes related to membrane remodeling and dynamics. Whether BAR domain proteins are involved in sculpting membranes in specific submitochondrial compartments is largely unknown. In this study, we report FAM92A1 as a novel BAR domain protein localizes to the matrix side of the MIM. Loss of FAM92A1 caused a severe disruption to mitochondrial morphology and ultrastructure, impairing organelle bioenergetics. Furthermore, FAM92A1 displayed a membrane-remodeling activity in vitro, inducing a high degree of membrane curvature. Collectively, our findings uncover a role for a BAR domain protein as a critical organizer of the mitochondrial ultrastructure that is indispensable for mitochondrial function.

Download Full-text