Disease relevance of Rab43

• Rab GGTase inhibition may represent a new treatment for thrombocytosis and clotting disorders [1].
• Live Salmonella modulate expression of Rab proteins to persist in a specialized compartment and escape transport to lysosomes [2].
• Second, the position of the nitrogen in the side chain of phosphonocarboxylates is crucial for their ability to inhibit Rab prenylation and hence to inhibit bone resorption [3].
• Since proteins belonging to the Rab family have already been related to retinal degeneration we considered RAB23 an interesting candidate for the RP25 locus [4].

High impact information on Rab43

• The Rab family of low-molecular-mass GTP-binding proteins are thought to guide membrane fusion between a transport vesicle and the target membrane, and to determine the specificity of docking [5].
• In brain, the Rab protein Rab3A is specific to synaptic vesicles, whose exocytosis can be monitored with submillisecond resolution by following synaptic transmission [5].
• The Rab GTPase effector Noc2 was brought into the limelight by a recent publication that demonstrated its requirements at different stages of regulated exocytosis [6].
• REP1 is involved in lipid modification (prenylation) of Rab GTPases, key regulators of intracellular vesicular transport and organelle dynamics [7].
• Heterozygous-null females exhibit characteristic hallmarks of CHM: progressive degeneration of the photoreceptors, patchy depigmentation of the RPE, and Rab prenylation defects [7].

Biological context of Rab43

• This work identifies a key role for the Rab38/Rab32 subfamily of Rab proteins in the biogenesis of melanosomes and potentially other lysosome-related organelles [8].
• Our data provide the first evidence for a dual role of a Rab GTPase in regulating both generation and turnover of PIs via PI kinases and phosphatases to coordinate signaling functions with organelle homeostasis [9].
• Screening its possible Rab partner by a yeast two-hybrid system revealed that an amino-terminal zinc-finger domain of granuphilin interacts with Rab27a [10].
• These Rab proteins regulate the endocytosis and recycling or degradation of activated receptor tyrosine kinases such as the platelet-derived growth factor receptor (PDGFR) [11].
• Rabphilin is a membrane trafficking protein on secretory vesicles that consists of an N-terminal Rab-binding domain and C-terminal tandem C2 domains [12].

Anatomical context of Rab43

• These results provide the first molecular description of an organelle receptor for an actin-based motor, illustrate how alternate exon usage can be used to specify cargo, and further expand the functional repertoire of Rab GTPases and their effectors [13].
• Rab GTPases are regulators of intracellular membrane traffic [14].
• The association of Rab27b with fusiform vesicles and its differentiation-dependent expression suggest that this Rab protein plays a role in regulating the delivery of fusiform vesicles to the apical plasma membrane of umbrella cells [15].
• Rab function is regulated by GDP dissociation inhibitor (GDI), which releases Rab proteins from membranes and inhibits GDP dissociation [16].
• A novel set of Rab and its effector, Rab27a/granuphilin, which is localized on insulin granules in pancreatic beta cells, was recently identified [17].

Associations of Rab43 with chemical compounds

• Guanine nucleotide exchange is essential for Rab GTPase activities in regulating intracellular vesicle trafficking [18].
• The importance of the Rab family of small GTPases (guanosine 5'-triphosphatases) in platelet biogenesis is revealed in gunmetal (gm/gm) mice, which show deficient Rab isoprenylation and macrothrombocytopenia with few granules and abnormal megakaryocyte morphology [19].
• Rab proteins typically lack the consensus carboxyl-terminal CXXX motif that signals isoprenoid modification of Ras and other isoprenylated proteins and, instead, terminate in either CC or CXC sequences (C = cysteine, X = any amino acid) [20].
• Contrary to the cytosolic localization of all known GDI proteins, acting on Rab or Rho, RhoGDI-3 is associated to a Triton X-100-insoluble membranous or cytoskeletal subcellular fraction [21].
• Our results suggest that homotypic fusion of ER membranes requires Rab and that Rab activation is a transient event necessary for the formation of a fusion pore leading to the mixing of luminal contents of ER microsomes [22].

Analytical, diagnostic and therapeutic context of Rab43

• We report here the molecular cloning and characterization of a novel Rab protein, Rab33B [23].
• The complexity of the Rab and Rho GTP-binding protein subfamilies revealed by a PCR cloning approach [24].
• To localize Rab GDI, we processed cells from different sources for indirect immunofluorescence microscopy [25].

References