scholarly journals Darkness descends with two Rabs

2006 ◽  
Vol 175 (2) ◽  
pp. 199-200 ◽  
Author(s):  
Michael S. Marks
Keyword(s):  
Vesicular Transport ◽  
Rab Proteins ◽  
Rab Gtpases ◽  
Tissue Specific ◽  
Vacuolar System ◽  
Redundant Role

Over 60 distinct Rab GTPases regulate specific vesicular transport steps in the mammalian central vacuolar system. Wasmeier et al. (this issue, p. 271) reveal a redundant role for two tissue-specific Rab proteins in regulating transport to a tissue-specific lysosome-related organelle, the melanosome.

scholarly journals Structures ofDrosophila melanogasterRab2 and Rab3 bound to GMPPNP

2015 ◽  
Vol 71 (1) ◽  
pp. 34-40 ◽  
Author(s):  
Jennifer A. Lardong ◽  
Jan H. Driller ◽  
Harald Depner ◽  
Christoph Weise ◽  
Astrid Petzoldt ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Intracellular Trafficking ◽  
Large Family ◽  
Cysteine Residue ◽  
Effector Proteins ◽  
Rab Proteins ◽  
Rab Gtpases ◽  
Ras Proteins ◽  
Transport Vesicles ◽  
Switch Regions

Rab GTPases belong to the large family of Ras proteins. They act as key regulators of membrane organization and intracellular trafficking. Functionally, they act as switches. In the active GTP-bound form they can bind to effector proteins to facilitate the delivery of transport vesicles. Upon stimulation, the GTP is hydrolyzed and the Rab proteins undergo conformational changes in their switch regions. This study focuses on Rab2 and Rab3 fromDrosophila melanogaster. Whereas Rab2 is involved in vesicle transport between the Golgi and the endoplasmatic reticulum, Rab3 is a key player in exocytosis, and in the synapse it is involved in the assembly of the presynaptic active zone. Here, high-resolution crystal structures of Rab2 and Rab3 in complex with GMPPNP and Mg2+are presented. In the structure of Rab3 a modified cysteine residue is observed with an enigmatic electron density attached to its thiol function.

The role of host cell Rab GTPases in influenza A virus infections

2021 ◽  
Author(s):  
Jing Wu ◽  
Jiaqi Gu ◽  
Li Shen ◽  
Xiaonan Jia ◽  
Yiqian Yin ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Respiratory Infections ◽  
Small Gtpase ◽  
Regulatory Mechanisms ◽  
Rab Proteins ◽  
Rab Gtpases ◽  
Virus Infections ◽  
Adaptation Mechanisms

Influenza A virus (IAV) is a crucial cause of respiratory infections in humans worldwide. Therefore, studies should clarify adaptation mechanisms of IAV and critical factors of the viral pathogenesis in human hosts. GTPases of the Rab family are the largest branch of the Ras-like small GTPase superfamily, and they regulate almost every step during vesicle-mediated trafficking. Evidence has shown that Rab proteins participate in the lifecycle of IAV. In this mini-review, we outline the regulatory mechanisms of different Rab proteins in the lifecycle of IAV. Understanding the role of Rab proteins in IAV infections is important to develop broad-spectrum host-targeted antiviral strategies.

scholarly journals A novel function for Rab proteins during maturation of secretory granules

2021 ◽  
Author(s):  
Sarah D Neuman ◽  
Annika R Lee ◽  
Jane E Selegue ◽  
Amy T Cavanagh ◽  
Arash Bashirullah
Keyword(s):  
Salivary Glands ◽  
Secretory Granule ◽  
Secretory Granules ◽  
Secretory Cells ◽  
Rab Proteins ◽  
Dependent Manner ◽  
Rab Gtpases ◽  
Cargo Proteins ◽  
Granule Maturation ◽  
Granule Growth

Regulated exocytosis is an essential process whereby professional secretory cells synthesize and secrete specific cargo proteins in a stimulus-dependent manner. Cargo-containing secretory granules are synthesized in the trans-Golgi Network (TGN); after budding from the TGN, granules undergo many modifications, including a dramatic increase in size. These changes occur during a poorly understood process called secretory granule maturation. Here we leverage the professional secretory cells of the Drosophila larval salivary glands as a model system to characterize a novel and unexpected role for Rab GTPases during secretory granule maturation. We find that secretory granules in the larval salivary glands increase in size ~300-fold between biogenesis and release, and loss of Rab1 or Rab11 dramatically reduces granule size. Surprisingly, we find that Rab1 and Rab11 protein localize to secretory granule membranes. Rab11 associates with granule membranes throughout the maturation process, and Rab11 is required for recruitment of Rab1. In turn, Rab1 associates specifically with immature secretory granules and drives granule growth. In addition to their roles in granule growth, both Rab1 and Rab11 appear to have additional roles during exocytosis; Rab11 function is necessary for exocytosis, while the presence of Rab1 on immature granules may prevent precocious exocytosis. Overall, these results highlight a new and unexpected role for Rab GTPases in secretory granule maturation.

scholarly journals Back to the future: new target-validated Rab antibodies for evaluating LRRK2 signalling in cell biology and Parkinson's disease

2018 ◽  
Vol 475 (1) ◽  
pp. 185-189 ◽  
Author(s):  
Patrick A. Eyers
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Biology ◽  
Human Neutrophils ◽  
Rab Proteins ◽  
Rab Gtpases ◽  
Biochemical Journal ◽  
The Future ◽  
Brain Extracts ◽  
Sporadic Cases

The addition of phosphate groups to substrates allows protein kinases to regulate a myriad of biological processes, and contextual analysis of protein-bound phosphate is important for understanding how kinases contribute to physiology and disease. Leucine-rich repeat kinase 2 (LRRK2) is a Ser/Thr kinase linked to familial and sporadic cases of Parkinson's disease (PD). Recent work established that multiple Rab GTPases are physiological substrates of LRRK2, with Rab10 in particular emerging as a human substrate whose site-specific phosphorylation mirrors hyperactive LRRK2 lesions associated with PD. However, current assays to quantify Rab10 phosphorylation are expensive, time-consuming and technically challenging. In back-to-back studies reported in the Biochemical Journal, Alessi and colleagues teamed up with clinical colleagues and collaborators at the Michael J. Fox Foundation (MJFF) for Parkinson's research to develop, and validate, a panel of exquisitely sensitive phospho-specific Rab antibodies. Of particular interest, the monoclonal antibody-designated MJFF-pRAB10 detects phosphorylated Rab 10 on Thr73 in a variety of cells, brain extracts, PD-derived samples and human neutrophils, the latter representing a previously unrecognised biological resource for LRRK2 signalling analysis. In the future, these antibodies could become universal resources in the fight to understand and quantify connections between LRRK2 and Rab proteins, including those associated with clinical PD.

scholarly journals The Rab-Rabphilin system in injured human podocytes stressed by glucose overload and angiotensin II

2020 ◽  
Vol 319 (2) ◽  
pp. F178-F191 ◽  
Author(s):  
Olga Martinez-Arroyo ◽  
Ana Ortega ◽  
Javier Perez-Hernandez ◽  
Felipe J. Chaves ◽  
Josep Redon ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Expression Patterns ◽  
Mrna Level ◽  
Vesicular Transport ◽  
Kidney Injury ◽  
Rab Gtpases ◽  
Protein Levels ◽  
Differentiated Cells ◽  
Filtration Barrier ◽  
The Impact

Kidney injury in hypertension and diabetes entails, among in other structures, damage in a key cell of the glomerular filtration barrier, the podocyte. Podocytes are polarized and highly differentiated cells in which vesicular transport, partly driven by Rab GTPases, is a relevant process. The aim of the present study was to analyze Rab GTPases of the Rab-Rabphilin system in human immortalized podocytes and the impact of high glucose and angiotensin II. Furthermore, alterations of the system in urine cell pellets from patients with hypertension and diabetes were studied. Apoptosis was analyzed in podocytes, and mRNA level quantification, Western blot analysis, and immunofluorescence were developed to quantify podocyte-specific molecules and Rab-Rabphilin components (Rab3A, Rab27A, and Rabphilin3A). Quantitative RT-PCR was performed on urinary cell pellet from patients. The results showed that differentiated cells had reduced protein levels of the Rab-rabphillin system compared with undifferentiated cells. After glucose overload and angiotensin II treatment, apoptosis was increased and podocyte-specific proteins were reduced. Rab3A and Rab27A protein levels were increased under glucose overload, and Rabphilin3A decreased. Furthermore, this system exhibited higher levels under stress conditions in a manner of angiotensin II dose and time treatment. Immunofluorescence imaging indicated different expression patterns of podocyte markers and Rab27A under treatments. Finally, Rab3A and Rab27A were increased in patient urine pellets and showed a direct relationship with albuminuria. Collectively, these results suggest that the Rab-Rabphilin system could be involved in the alterations observed in injured podocytes and that a mechanism may be activated to reduce damage through the vesicular transport enhancement directed by this system.

A model for Rab GTPase localization

2005 ◽  
Vol 33 (4) ◽  
pp. 627-630 ◽  
Author(s):  
S. Pfeffer
Keyword(s):  
Steady State ◽  
Cellular Localization ◽  
Rab Gtpase ◽  
Rab Proteins ◽  
Rab Gtpases ◽  
Macromolecular Assemblies ◽  
Complex Interactions ◽  
Membrane Compartment ◽  
Membrane Bound ◽  
Distinct Membrane

The human genome encodes almost 70 Rab GTPases. These proteins are C-terminally geranylgeranylated and are localized to the surfaces of distinct membrane-bound compartments in eukaryotic cells. This mini review presents a working model for how Rabs achieve and maintain their steady-state localizations. Data from a number of laboratories suggest that Rabs participate in the generation of macromolecular assemblies that generate functional microdomains within a given membrane compartment. Our data suggest that these complex interactions are important for the cellular localization of Rab proteins at steady state.

scholarly journals Rab GTPases: Emerging Oncogenes and Tumor Suppressive Regulators for the Editing of Survival Pathways in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 259 ◽  
Author(s):  
Priya D. Gopal Krishnan ◽  
Emily Golden ◽  
Eleanor A. Woodward ◽  
Nathan J. Pavlos ◽  
Pilar Blancafort
Keyword(s):  
Membrane Trafficking ◽  
Molecular Mechanisms ◽  
Intracellular Localization ◽  
Cellular Migration ◽  
Rab Gtpase ◽  
Rab Proteins ◽  
Rab Gtpases ◽  
Aberrant Expression ◽  
Post Translational Modifications ◽  
Survival Pathways

The Rab GTPase family of proteins are mediators of membrane trafficking, conferring identity to the cell membranes. Recently, Rab and Rab-associated factors have been recognized as major regulators of the intracellular positioning and activity of signaling pathways regulating cell growth, survival and programmed cell death or apoptosis. Membrane trafficking mediated by Rab proteins is controlled by intracellular localization of Rab proteins, Rab-membrane interactions and GTP-activation processes. Aberrant expression of Rab proteins has been reported in multiple cancers such as lung, brain and breast malignancies. Mutations in Rab-coding genes and/or post-translational modifications in their protein products disrupt the cellular vesicle trafficking network modulating tumorigenic potential, cellular migration and metastatic behavior. Conversely, Rabs also act as tumor suppressive factors inducing apoptosis and inhibiting angiogenesis. Deconstructing the signaling mechanisms modulated by Rab proteins during apoptosis could unveil underlying molecular mechanisms that may be exploited therapeutically to selectively target malignant cells.

scholarly journals Two-pore channels at the intersection of endolysosomal membrane traffic

2015 ◽  
Vol 43 (3) ◽  
pp. 434-441 ◽  
Author(s):  
Jonathan S. Marchant ◽  
Sandip Patel
Keyword(s):  
Nicotinic Acid ◽  
Traffic Flow ◽  
Rab Proteins ◽  
Rab Gtpases ◽  
Ion Permeation ◽  
Voltage Gated ◽  
Proteomic Data ◽  
Flow Through ◽  
Acidic Organelles

Two-pore channels (TPCs) are ancient members of the voltage-gated ion channel superfamily that localize to acidic organelles such as lysosomes. The TPC complex is the proposed target of the Ca2+-mobilizing messenger NAADP, which releases Ca2+ from these acidic Ca2+ stores. Whereas details of TPC activation and native ion permeation remain unclear, a consensus has emerged around their function in regulating endolysosomal trafficking. This role is supported by recent proteomic data showing that TPCs interact with proteins controlling membrane organization and dynamics, including Rab GTPases and components of the fusion apparatus. Regulation of TPCs by PtdIns(3,5)P2 and/or NAADP (nicotinic acid adenine dinucleotide phosphate) together with their functional and physical association with Rab proteins provides a mechanism for coupling phosphoinositide and trafficking protein cues to local ion fluxes. Therefore, TPCs work at the regulatory cross-roads of (patho)physiological cues to co-ordinate and potentially deregulate traffic flow through the endolysosomal network. This review focuses on the native role of TPCs in trafficking and their emerging contributions to endolysosomal trafficking dysfunction.

Rab GTPases in vesicular transport

1993 ◽  
Vol 5 (4) ◽  
pp. 613-620 ◽  
Author(s):  
Marino Zerial ◽  
Harald Stenmark
Keyword(s):  
Vesicular Transport ◽  
Rab Gtpases

scholarly journals FgRab5 and FgRab7 are essential for endosomes biogenesis and non-redundantly recruit the retromer complex to the endosomes in Fusarium graminearum

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Yakubu Saddeeq Abubakar ◽  
Han Qiu ◽  
Wenqin Fang ◽  
Huawei Zheng ◽  
Guodong Lu ◽  
...  
Keyword(s):  
Fusarium Graminearum ◽  
Retrograde Transport ◽  
Small Gtpases ◽  
Rab Proteins ◽  
Rab Gtpases ◽  
Wild Type ◽  
Retromer Complex ◽  
Cargo Proteins ◽  
Endosomal Membranes ◽  
In The Wild

AbstractThe retromer complex, composed of the cargo-selective complex (CSC) Vps35-Vps29-Vps26 in complex with the sorting nexin dimer Vps5-Vps17, mediates the sorting and retrograde transport of cargo proteins from the endosomes to the trans-Golgi network in eukaryotic cells. Rab proteins belong to the Ras superfamily of small GTPases and regulate many trafficking events including vesicle formation, budding, transport, tethering, docking and fusion with target membranes. Herein, we investigated the potential functional relationship between the retromer complex and the 11 Rab proteins that exist in Fusarium graminearum using genetic and high-resolution laser confocal microscopic approaches. We found that only FgRab5 (FgRab5A and FgRab5B) and FgRab7 associate with the retromer complex. Both FgVps35-GFP and FgVps17-GFP are mis-localized and appear diffused in the cytoplasm of ΔFgrab5A, ΔFgrab5B and ΔFgrab7 mutants as compared to their punctate localization within the endosomes of the wild-type. FgRab7 and FgRab5B were found to co-localize with the retromer on endosomal membranes. Most strikingly, we found that these three Rab GTPases are indispensable for endosome biogenesis as both early and late endosomes could not be detected in the cells of the mutants after FM4-64 staining of the cells, while they were very clearly seen in the wild-type PH-1. Furthermore, FgRab7 was found to recruit FgVps35 but not FgVps17 to the endosomal membranes, whereas FgRab5B recruits both FgVps35 and FgVps17 to the membranes. Thus, we conclude that the Rab proteins FgRab5A, FgRab5B and FgRab7 play critical roles in the biogenesis of endosomes and in regulating retromer-mediated trafficking in F. graminearum.

Sign in / Sign up

Export Citation Format

Share Document