A Proximity MAP of RAB GTPases DOI Creative Commons

Véronique Gaudeault St-Laurent,

Benoît Marchand,

Raphaëlle Larcher

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

ABSTRACT RAB GTPases are the most abundant family of small and regulate multiple aspects membrane trafficking events, from cargo sorting to vesicle budding, transport, docking, fusion. To these processes, RABs tightly regulated by guanine exchange factors (GEFs) GTPase-activating proteins (GAPs). Activated recruit effector that trafficking. Identifying RAB-associated has proven be difficult because their association with interacting is often transient. Recent advances in proximity labeling approaches allow for covalent neighbors interest now permit cataloging vicinity GTPases. Here, we report APEX2 23 human neighboring proteomes. We have used bioinformatic analyses map specific proximal an extensive array GTPases, localization can inferred adjacent proteins. Focusing on examples, identified a physical interaction between RAB25 DENND6A, which affects cell migration. also show functional relationships RAB14 EARP complex, or SHIP164 its close ortholog UHRF1BP1. Our dataset provides resource community helps define novel connections

Language: Английский

The small GTPase MRAS is a broken switch DOI Creative Commons

Gabriela Bernal Astrain,

Regina Strakhova,

Chang Hwa Jo

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 14, 2025

Intense research on founding members of the RAS superfamily has defined our understanding these critical signalling proteins, leading to premise that small GTPases function as molecular switches dependent differential nucleotide loading. The closest homologs H/K/NRAS are three-member RRAS family, and interest in MRAS GTPase a regulator MAPK activity recently intensified. We show here does not classical switch is unable exchange GDP-to-GTP solution or when tethered lipid bilayer. defect unaffected by inclusion GEF SOS1 conserved distal ortholog from nematodes. Synthetic activating mutations widely used study presumed GTP-loaded state do increase exchange, but instead drive effector binding due sampling an activated conformation GDP-loaded state. This includes nucleation SHOC2-PP1Cα holophosphatase complex. Acquisition NMR spectra isotopically labeled live cells validated remains fully GDP-loaded, even supposed mutant. These data GTPases, including those most similar KRAS, have disparate biochemical activities challenge current dogma MRAS, suggesting previous may need reinterpretation. Small family classically switches, adopting off conformations bound nucleotides. Here authors reveal closely related archetypal RAS, completely deficient GTP exchange.

Language: Английский

Citations

0

The PACT Network: PRL, ARL, CNNM, and TRPM Proteins in Magnesium Transport and Disease DOI Open Access
Jeffery T. Jolly, Jessica S. Blackburn

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1528 - 1528

Published: Feb. 12, 2025

Magnesium, the most abundant divalent metal within cell, is essential for physiological function and critical in cellular signaling. To maintain homeostasis, intracellular magnesium levels are tightly regulated, as dysregulation linked to numerous diseases, including cancer, diabetes, cardiovascular disorders, neurological conditions. Over past two decades, extensive research on magnesium-regulating proteins has provided valuable insight into their pathogenic therapeutic potential. This review explores an emerging mechanism of homeostasis involving PRL (phosphatase regenerating liver), ARL (ADP ribosylation factor-like GTPase family), CNNM (cyclin cystathionine β-synthase domain transport mediator), TRPM (transient receptor potential melastatin) families, collectively termed herein PACT network. While each protein been studied its individual signaling disease contexts, interactions suggest a broader regulatory network with consolidates current knowledge proteins' structure, function, identifies gaps encourage future investigation. As field continues advance, understanding offers new opportunities basic development targeting magnesium-related disorders.

Language: Английский

Citations

0

ER nests are specialized ER subdomains in Arabidopsis where peroxisomes and lipid droplets form DOI
Zachary J. Wright, Nathan E. Tharp, Bonnie Bartel

et al.

Developmental Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0

Announcing the JCS–David Stephens Prize and the 2024 winner Anja Konietzny DOI
Michael Way

Journal of Cell Science, Journal Year: 2025, Volume and Issue: 138(7)

Published: April 1, 2025

Language: Английский

Citations

0

Mapping the MOB proteins’ proximity network reveals a unique interaction between human MOB3C and the RNase P complex DOI Creative Commons
Islam E. Elkholi, Jonathan Boulais, Marie‐Pier Thibault

et al.

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(9), P. 105123 - 105123

Published: Aug. 1, 2023

Distinct functions mediated by members of the monopolar spindle-one-binder (MOB) family proteins remain elusive beyond evolutionarily conserved and well-established roles MOB1 (MOB1A/B) in regulating tissue homeostasis within Hippo pathway. Since MOB are adaptors, understanding how they engage protein-protein interactions help assemble complexes is essential to define full scope their biological functions. To address this, we undertook a proximity-dependent biotin identification approach interactomes all seven human HeLa embryonic kidney 293 cell lines. We uncovered >200 interactions, which at least 70% unreported on BioGrid. The generated dataset reliably recalled bona fide interactors well-studied MOBs. further defined common differential interactome between different MOBs subfamily an individual level. discovered unique association MOB3C 7 10 protein subunits RNase P complex, endonuclease that catalyzes tRNA 5' maturation. As proof principle for robustness dataset, validated specific interaction with catalytically active using affinity purification-mass spectrometry pre-tRNA cleavage assays pulldowns. In summary, our data provide novel insights into biology reveal first MOB3C, components hence exciting nexus RNA biology.

Language: Английский

Citations

2

The ARF GTPase regulatory network in collective invasion and metastasis DOI Creative Commons
Konstantina Nikolatou, David M. Bryant, Emma Sandilands

et al.

Biochemical Society Transactions, Journal Year: 2023, Volume and Issue: 51(4), P. 1559 - 1569

Published: Aug. 25, 2023

The ability to remodel and move cellular membranes, the cargoes regulated by these allows for specialised functions occur in distinct regions of cell a process known as polarisation. collectively co-ordinate such polarisation between cells genesis multicellularity, formation organs. During tumourigenesis, rules tissue become dysregulated, allowing collective polarity rearrangements that can drive metastasis. In this review, we focus on how membrane trafficking underpins invasion metastasis cancer. We examine through lens ADP-ribosylation factor (ARF) subfamily small GTPases, focusing ARF regulatory network - activators, inactivators, effectors, modifications controls GTPase function.

Language: Английский

Citations

2

First person – Laura Quirion DOI Creative Commons
Laura Quirion, Laura Quirion

Journal of Cell Science, Journal Year: 2024, Volume and Issue: 137(9)

Published: May 1, 2024

ABSTRACT First Person is a series of interviews with the first authors selection papers published in Journal Cell Science, helping researchers promote themselves alongside their papers. Laura Quirion author on ‘ Mapping global interactome ARF family reveals spatial organization cellular signaling pathways’, JCS. PhD candidate lab Jean-François Côté at Montreal Clinical Research Institute, Montréal, Canada, investigating dynamics GTPase signaling.

Language: Английский

Citations

0

SNX5-Rab11a protects against cardiac hypertrophy through regulating LRP6 membrane translocation DOI
Yutong Li, Xiang Wang,

Yaguang Bi

et al.

Journal of Molecular and Cellular Cardiology, Journal Year: 2024, Volume and Issue: 194, P. 46 - 58

Published: June 29, 2024

Language: Английский

Citations

0

A Proximity MAP of RAB GTPases DOI Creative Commons

Véronique Gaudeault St-Laurent,

Benoît Marchand,

Raphaëlle Larcher

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

ABSTRACT RAB GTPases are the most abundant family of small and regulate multiple aspects membrane trafficking events, from cargo sorting to vesicle budding, transport, docking, fusion. To these processes, RABs tightly regulated by guanine exchange factors (GEFs) GTPase-activating proteins (GAPs). Activated recruit effector that trafficking. Identifying RAB-associated has proven be difficult because their association with interacting is often transient. Recent advances in proximity labeling approaches allow for covalent neighbors interest now permit cataloging vicinity GTPases. Here, we report APEX2 23 human neighboring proteomes. We have used bioinformatic analyses map specific proximal an extensive array GTPases, localization can inferred adjacent proteins. Focusing on examples, identified a physical interaction between RAB25 DENND6A, which affects cell migration. also show functional relationships RAB14 EARP complex, or SHIP164 its close ortholog UHRF1BP1. Our dataset provides resource community helps define novel connections

Language: Английский

Citations

0