Rab GTPases at a glance

Schwartz, Samantha L.; Cao, Canhong; Pylypenko, Olena; Rak, Alexey; Wandinger‐Ness, Angela

doi:10.1242/jcs.015909

Cited by 349 publications

(305 citation statements)

References 109 publications

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“…Rab proteins are GTP-binding proteins that control the fusion of target membranes through GTP hydrolysis (Cai et al 2007;Schwartz et al 2007). The precise combination of Rab proteins and SNAREs determine the functional identity of numerous membrane compartments and guide fusion between donor and acceptor compartments (Pfeffer 2001;Murray et al 2002;Behnia and Munro 2005).…”

Section: Er Dynamics and Assemblymentioning

confidence: 99%

Endoplasmic Reticulum Structure and Interconnections with Other Organelles

English

Voeltz

2013

Cold Spring Harbor Perspectives in Biology

286

220

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The endoplasmic reticulum (ER) is a large, continuous membrane-bound organelle comprised of functionally and structurally distinct domains including the nuclear envelope, peripheral tubular ER, peripheral cisternae, and numerous membrane contact sites at the plasma membrane, mitochondria, Golgi, endosomes, and peroxisomes. These domains are required for multiple cellular processes, including synthesis of proteins and lipids, calcium level regulation, and exchange of macromolecules with various organelles at ER-membrane contact sites. The ER maintains its unique overall structure regardless of dynamics or transfer at ER-organelle contacts. In this review, we describe the numerous factors that contribute to the structure of the ER.T he endoplasmic reticulum (ER) is a dynamic organelle responsible for many cellular functions, including the synthesis of proteins and lipids, and regulation of intracellular calcium levels. This review focuses on the distinct and complex morphology of the ER. The structure of the ER is complex because of the numerous distinct domains that exist within one continuous membrane bilayer. These domains are shaped by interactions with the cytoskeleton, by proteins that stabilize membrane shape, and by a homotypic fusion machinery that allows the ER membrane to maintain its continuity and identity. The ER also contains domains that contact the plasma membrane (PM) and other organelles including the Golgi, endosomes, mitochondria, lipid droplets, and peroxisomes. ER contact sites with other organelles and the PM are both abundant and dispersed throughout the cytoplasm, suggesting that they too could influence the overall architecture of the ER. As we will discuss here, ER shape and distribution are regulated by many intrinsic and extrinsic forces. ER STRUCTURE AND FORMATION Domains of the ER Are Stabilized by Membrane-Shaping ProteinsThe endoplasmic reticulum (ER) is a large membrane-bound compartment spread throughout the cytoplasm of eukaryotic cells. It is divided into three major morphologies that include the nuclear envelope (NE), peripheral ER cisternae, and an interconnected tubular network

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Section: Er Dynamics and Assemblymentioning

confidence: 99%

Endoplasmic Reticulum Structure and Interconnections with Other Organelles

English

Voeltz

2013

Cold Spring Harbor Perspectives in Biology

286

220

View full text Add to dashboard Cite

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“…In general, Rab functions as a molecular switch by cycling between a guanosine diphosphate (GDP)-bound state and a GTP-bound state, and the GTP-bound active form promotes membrane traffic through interaction with a specific effector molecule (Grosshans et al, 2006;Schwartz et al, 2007). The best characterized Rab isoform in melanocytes is Rab27A, which is involved in melanosome transfer from microtubules to actin filaments through interaction with the melanocyte-specific effector Slac2-a/melanophilin Wu et al, 2002;Kuroda et al, 2003;Hume et al, 2006;reviewed in Fukuda, 2005) and melanosome anchoring to the plasma membrane through interaction with another Rab27A effector, Slp2-a (Kuroda and Fukuda, 2004).…”

Section: Introductionmentioning

confidence: 99%

Varp Is a Novel Rab32/38-binding Protein That Regulates Tyrp1 Trafficking in Melanocytes

Tamura

Ohbayashi

Maruta

et al. 2009

MBoC

182

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Two small GTPase Rabs, Rab32 and Rab38, have recently been proposed to regulate trafficking of melanogenic enzymes to melanosomes in mammalian epidermal melanocytes; however, the exact molecular mechanism of Rab32/38-mediated transport of melanogenic enzymes has never been clarified, because no Rab32/38-specific effector has ever been identified. In this study, we screened for a Rab32/38-specific effector by a yeast two-hybrid assay using a guanosine triphosphate (GTP)-locked Rab32/38 as bait and found that VPS9-ankyrin-repeat protein (Varp)/Ankrd27, characterized previously as a guanine nucleotide exchange factor (GEF) for Rab21, functions as a specific Rab32/38-binding protein in mouse melanocyte cell line melan-a. Deletion analysis showed that the first ankyrin-repeat (ANKR1) domain functions as a GTP-dependent Rab32/38-binding domain, but that the N-terminal VPS9 domain (i.e., Rab21-GEF domain) does not. Small interfering RNA-mediated knockdown of endogenous Varp in melan-a cells caused a dramatic reduction in Tyrp1 (tyrosinase-related protein 1) signals from melanosomes but did not cause any reduction in Pmel17 signals. Furthermore, expression of the ANKR1 domain in melan-a cells also caused a dramatic reduction of Tyrp1 signals, whereas the VPS9 domain had no effect. Based on these findings, we propose that Varp functions as the Rab32/38 effector that controls trafficking of Tyrp1 in melanocytes.

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“…Guanine nucleotide dissociation inhibitors recycle GDP-bound Rabs back to the cytosol. GTP-bound Rabs recruit other proteins called effectors, forming protein complexes that tether the transport vesicle to the acceptor membrane (7)(8)(9)(10)(11), and participate in the priming of synaptic vesicles to a readily releasable state (12).…”

mentioning

confidence: 99%

Rab27 and Rab3 sequentially regulate human sperm dense-core granule exocytosis

Bustos

Lucchesi

Ruete

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Two so-called “secretory Rabs,” Rab3 and Rab27, regulate late steps during dense-core vesicle exocytosis in neuroendocrine cells. Sperm contain a single large dense-core granule that is released by regulated exocytosis (termed the acrosome reaction) during fertilization or on exposure to inducers in vitro. Sperm exocytosis uses the same fusion machinery as neurons and neuroendocrine cells, with an additional requirement for active Rab3. Here we show that Rab27 is also required for the acrosome reaction, as demonstrated by the inability of inducers to elicit exocytosis when streptolysin O-permeabilized human sperm were loaded with inhibitory anti-Rab27 antibodies or the Rab27–GTP binding domain of the effector Slac2-b. The levels of GTP-bound Rab27 increased on initiation of exocytosis, as did the proportion of GTP-bound Rab3A. We have developed a fluorescence microscopy-based method for detecting endogenous Rab3A-GTP and Rab27-GTP in the acrosomal region of human sperm. Challenge with an inducer increased the population of cells exhibiting GTP-bound Rabs in this subcellular domain. Interestingly, introducing recombinant Rab27A loaded with GTP-γ-S into sperm elicited a remarkable increase in the number of cells evincing GTP-bound Rab3A. In the converse condition, recombinant Rab3A did not modify the percentage of Rab27-GTP–containing cells. Furthermore, Rab27A-GTP recruited a Rab3 GDP/GTP exchange factor (GEF) activity. Our findings suggest that Rab27/Rab3A constitutes a Rab-GEF cascade in dense-core vesicle exocytosis.

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Rab GTPases at a glance

Cited by 349 publications

References 109 publications

Endoplasmic Reticulum Structure and Interconnections with Other Organelles

Endoplasmic Reticulum Structure and Interconnections with Other Organelles

Varp Is a Novel Rab32/38-binding Protein That Regulates Tyrp1 Trafficking in Melanocytes

Rab27 and Rab3 sequentially regulate human sperm dense-core granule exocytosis

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