Identification of rabaptin‐5, rabex‐5, and GM130 as putative effectors of rab33b, a regulator of retrograde traffic between the Golgi apparatus and ER

Valsdottir, Rebekka; Hashimoto, Hitoshi; Ashman, Keith; Koda, Toshiaki; Storrie, Brian; Nilsson, Tommy

doi:10.1016/s0014-5793(01)02993-3

Cited by 98 publications

(99 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This raises the possibility that the Rab5 GEFs Rabex-5 and Rin1 may also function as Rab11B GEFs, hence coupling the Rab5-and Rab11-regulated endocytic recycling activities (Bucci et al, 1994;Schlierf et al, 2000), as has been observed for yeast GEFs linking exocytic Rabs (Wang and Ferro-Novick, 2002). Similarly, the expression profile of Rabaptin-5 (Ohya et al, 1998) showed a stronger correlation with Rab33B than with Rab5 isoforms (Figure 2), consistent with the recent biochemical evidence that Rabaptin-5 also interacts with Rab33B (Valsdottir et al, 2001). We also noted that TRAPPC4, a mammalian homologue to a component of the Ypt1/Rab1 specific yeast GEF Trapp complex (Jones et al, 2000), clustered with Rab1B/C, suggestive of an evolutionary conserved function in the Rab1 hub in early exocytic pathways of mammalian cells.…”

Section: Rab Regulators Rab Gtpases Do Not Function In Isolationsupporting

confidence: 88%

Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome

Gürkan

Lapp

Alory

et al. 2005

MBoC

115

107

View full text Add to dashboard Cite

Rab GTPases and SNARE fusion proteins direct cargo trafficking through the exocytic and endocytic pathways of eukaryotic cells. We have used steady state mRNA expression profiling and computational hierarchical clustering methods to generate a global overview of the distribution of Rabs, SNAREs, and coat machinery components, as well as their respective adaptors, effectors, and regulators in 79 human and 61 mouse nonredundant tissues. We now show that this systems biology approach can be used to define building blocks for membrane trafficking based on Rab-centric protein activity hubs. These Rab-regulated hubs provide a framework for an integrated coding system, the membrome network, which regulates the dynamics of the specialized membrane architecture of differentiated cells. The distribution of Rab-regulated hubs illustrates a number of facets that guides the overall organization of subcellular compartments of cells and tissues through the activity of dynamic protein interaction networks. An interactive website for exploring datasets comprising components of the Rab-regulated hubs that define the membrome of different cell and organ systems in both human and mouse is available at http://www.membrome.org/. INTRODUCTIONUnderstanding the molecular basis for the organization of the exocytic and endocytic membrane trafficking pathways in the eukaryotic cell remains a formidable challenge. The foundation of these pathways is the lipid bilayer that separates different subcellular compartments, their distinguishing features encoded by phospholipid composition, and unique sets of integral and peripheral membrane proteins. By harnessing and regulating the fundamental processes of membrane fission and fusion through the action of protein complexes, the lipid bilayer can be exploited to produce a variety of distinct subcellular compartments with unique chemical environments that play essential roles in cell and organ function. Moreover, it is now evident that these subcellular compartments are dynamic structures in continuous and specific communication through carrier vesicles and tubules that mobilize cargo to specific destinations. They can be disassembled and reassembled in a remarkably facile manner in response to cell signaling pathways, mitosis, or by simple chemical perturbants.Implicit in these dynamic pathways is the need to systematically and reversibly regulate protein interactions. Although traditional phylogenetic analyses provided significant insights into the diversity of components that direct membrane traffic (Pereira-Leal and Seabra, 2000;Chen and Scheller, 2001;Pereira-Leal and Seabra, 2001), our understanding of the basic cellular building blocks that organize this diversity into contiguous pathways is still fragmentary. Reductionist approaches using biochemical and molecular tools also provide important insights into specific steps of a pathway. However, understanding the global interconnectivities of complex biological pathways, such as cargo trafficking, will require new approaches utilizing modern ...

show abstract

Section: Rab Regulators Rab Gtpases Do Not Function In Isolationsupporting

confidence: 88%

Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome

Gürkan

Lapp

Alory

et al. 2005

MBoC

115

107

View full text Add to dashboard Cite

show abstract

“…Thus, the observed effects of RUTBC1 knockdown on tyrosinase/Tyrp1/Dct signals are most likely attributable to excess activation of Rab32/38, rather than of Rab33B. However, because Rab33B has been shown to be involved in the autophagosome maturation step (22,38) and the retrograde Golgi transport pathway (39), and because decreased tyrosinase signals were observed in Rab33B(Q92L)-expressing cells, Rab33B may participate in melanogenic enzyme trafficking in melanocytes in a different way from Rab32/38, i.e. by regulating autophagy or retrograde Golgi transport.…”

Section: Discussionmentioning

confidence: 99%

RUTBC1 Functions as a GTPase-activating Protein for Rab32/38 and Regulates Melanogenic Enzyme Trafficking in Melanocytes

Marubashi

Shimada

Fukuda

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Two cell type-specific Rab proteins, Rab32 and Rab38 (Rab32/38), have been proposed as regulating the trafficking of melanogenic enzymes, including tyrosinase and tyrosinase-related protein 1 (Tyrp1), to melanosomes in melanocytes. Like other GTPases, Rab32/38 function as switch molecules that cycle between a GDP-bound inactive form and a GTP-bound active form; the cycle is thought to be regulated by an activating enzyme, guanine nucleotide exchange factor (GEF), and an inactivating enzyme, GTPase-activating protein (GAP), which stimulates the GTPase activity of Rab32/38. Although BLOC-3 has already been identified as a Rab32/38-specific GEF that regulates the trafficking of tyrosinase and Tyrp1, no physiological GAP for Rab32/38 in melanocytes has ever been identified, and it has remained unclear whether Rab32/38 is involved in the trafficking of dopachrome tautomerase, another melanogenic enzyme, in mouse melanocytes. In this study we investigated RUTBC1, which was originally characterized as a Rab9-binding protein and GAP for Rab32 and Rab33B in vitro, and the results demonstrated that RUTBC1 functions as a physiological GAP for Rab32/38 in the trafficking of all three melanogenic enzymes in mouse melanocytes. The results of this study also demonstrated the involvement of Rab9A in the regulation of the RUTBC1 localization and in the trafficking of all three melanogenic enzymes. We discovered that either excess activation or inactivation of Rab32/38 achieved by manipulating RUTBC1 inhibits the trafficking of all three melanogenic enzymes. These results collectively indicate that proper spatiotemporal regulation of Rab32/38 is essential for the trafficking of all three melanogenic enzymes in mouse melanocytes.

show abstract

“…For example, the Rab5 effector EEA1 has been shown to bind syntaxin 6, a SNARE implicated in trafficking between the trans-Golgi network and early endosomes (45). In addition to binding Rab5, rabex-5 and rabaptin-5 directly interact with Rab33b, a GTPase implicated in retrograde transport from the Golgi to the endoplasmic reticulum (46,47). Recently, rabaptin-5 was reported to form a complex with rabphilin-3, a protein implicated in the control of exocytosis and endocytosis in the nerve terminal (48 -51).…”

Section: Discussionmentioning

confidence: 99%

Mammalian Suppressor of Sec4 Modulates the Inhibitory Effect of Rab15 during Early Endocytosis

Strick

Francescutti

Zhao

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

Rab15 is a novel endocyticEndocytosis of cell surface receptors regulates both the intensity and duration of receptor signaling by controlling the location of signaling interactions and the desensitization and recycling of activated receptors (reviewed in Refs. 1 and 2). Accordingly, endocytic compartments are highly specialized both in terms of their organization and function. The early/ sorting endosome is a major trafficking compartment from which several trafficking pathways emerge. Recently, Rab GTPases have emerged as potent regulators of membrane trafficking through early/sorting endosomes. Rabs do not regulate membrane trafficking per se but function as regulatory throttles impacting the kinetics of membrane transport steps through the recruitment of specific effectors that in turn mediate membrane transport (reviewed in Refs. 3-5). For example, Rab5 mediates the internalization and fusion of incoming endocytic vesicles in vivo (6 -8) and the homotypic fusion of endosomes in vitro (8 -12). Overexpression of the constitutively active GTP-bound mutant Rab5-Q79L in baby hamster kidney cells results in a dramatic increase in fluid phase and receptormediated endocytosis and leads to formation of enlarged early/ sorting endosomes. Conversely, overexpression of GDP-bound Rab5 (S34N) reduces endocytic uptake and results in the formation of a diffuse network of small endocytic vesicles (6 -8).Following activation on endosome membranes, Rab5-GTP drives the organization of a specialized membrane domain with distinct functional characteristics (13-15). Rab5-GTP forms this domain by recruiting the phosphatidylinositol 3-kinase hVPs34, which catalyzes the local production of PI-3-phosphate (PI3P) 1 (16 -18). Rab5-GTP and hVPs34 activities are essential for the subsequent recruitment of rabenosyn-5 and the docking protein early endosome antigen (EEA1) to early endosomal membranes through PI3P (17-22). EEA1 also interacts directly with syntaxin 13, a SNARE implicated in the fusion of early endosomes (13,23). Thus a model is emerging in which Rab5-GTP functions as a regulatory protein, driving assembly of specific effector complexes on endosomal membranes leading to membrane fusion (24). Consistent with this model, the early endocytic GTPases, Rabs 4 and 11, have also been shown to organize into distinct domains on early endosomes through the local recruitment of effectors (14, 15). Moreover, Rab4 and Rab5 function are linked through the shared effectors rabaptin-5 (25) and rabenosyn-5 (15). Thus Rab-specific domains appear to coordinate endosomal trafficking directly by communicating via shared effector complexes.The early endocytic GTPase Rab15 exhibits distinct endocytic localization and activity. Rab15 distributes between two early endosomal compartments, colocalizing with Rabs 4 and 5 on early/sorting endosomes and with Rab11 on pericentriolar recycling endosomes (26). Overexpression of activated Rab15 (Rab15-GTP) inhibits both fluid phase and receptor-mediated endocytosis in vivo and the homotypic fusion of early e...

show abstract

Identification of rabaptin‐5, rabex‐5, and GM130 as putative effectors of rab33b, a regulator of retrograde traffic between the Golgi apparatus and ER

Cited by 98 publications

References 49 publications

Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome

Large-Scale Profiling of Rab GTPase Trafficking Networks: The Membrome

RUTBC1 Functions as a GTPase-activating Protein for Rab32/38 and Regulates Melanogenic Enzyme Trafficking in Melanocytes

Mammalian Suppressor of Sec4 Modulates the Inhibitory Effect of Rab15 during Early Endocytosis

Contact Info

Product

Resources

About