M C Seabra

..The human genome is predicted to contain 60 RAB genes, suggesting that future work could reveal further links between Rab dysfunction and disease...

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..The detailed understanding of these targeting mechanisms may allow future development of specific therapeutic agents that interfere with the function of each one of these proteins...

..A genetic defect in REP underlies human choroideremia, a disease of retinal degeneration...

..Our data suggest a model whereby REP behaves kinetically as an essential activator of the reaction...

..Comparisons of the amino acid sequences suggest that the proteins encoded by the Saccharomyces cerevisiae genes MAD2 and BET2 are the yeast counterparts of the mammalian Rab GG transferase alpha and beta subunits, respectively...

..Here we discuss recent insights into Rab prenylation and advances towards our understanding of both diseases...

..These results, together with recent data implicating myosinVa in the peripheral capture of melanosomes, suggest that Rab27a is necessary for the recruitment of myosinVa, so allowing the peripheral retention of melanosomes in melanocytes...

..The gene is located on chromosome 15q15-21.1, as determined by fluorescent in situ hybridization, and between markers D15S209 and AFM321ZD5 by radiation hybrid mapping...

..Rab27a plays a key role in the function of lysosomal-like organelles such as melanosomes in melanocytes and lytic granules in cytotoxic T lymphocytes. Little is known about Rab27b...

..The data imply the existence of multiple component A proteins, one of which is missing in choroideremia...

..Rab functional groups can help the understanding of the functional evolution of the Rab family in particular and vesicular transport in general, and may be used to predict general functions for novel Rab sequences...

..Recent results indicate that Rab cellular targeting might be Rab-dependent, and this paper briefly reviews our current knowledge of this process...

..This tissue and cell pattern of expression suggests that the VLDLR plays a role in the transport of VLDL or another plasma constituent from the vascular compartment to adjacent tissues...

..These results raise the possibility that the retinal degeneration in choroideremia results from the deficient geranylgeranylation of Ram/Rab27 or a closely related protein...

..Furthermore, the molecular switch property of Rabs may enable them to regulate the timing of the myosin association with the target organelle...

..Unraveling regulatory mechanisms responsible for melanosome motility in pigmented cells will provide general insights into organelles dynamics within eukaryotic cells...

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..These results suggest that Rab27 proteins, particularly Rab27b, play a crucial role in mast cell degranulation and that their action regulates the transition from microtubule to actin-based motility...

..Thus, melanophilin can associate simultaneously with activated Rab27a and myosin Va via distinct regions, and serve as a linker between these proteins...

..Our data suggest that up-regulated Rab27b in melanocytes of the Griscelli patient can partially take over the function of Rab27a, which could explain the fact that this patient had an evenly pigmented skin and was able to tan...

..EB1 appears to be non-essential to this process in cultured melanocytes, which suggests that it plays a redundant role and/or is required for melanocyte/keratinocyte contacts and melanosome transfer...

..These results suggest that Rab27a interacts with different classes of effector proteins in melanocytes and cytotoxic T lymphocytes...

..Therefore, NOX2 plays a critical role in conferring DCs the ability to function as specialized phagocytes adapted to process antigens rather than kill pathogens...

..Our results highlight the importance of the coiled-coil region together with R27BD and EFBD regions of Mlph in the formation of the active melanosomal Rab27a-Mlph-MyoVa complex...

..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...

..Our findings also imply that those Rabs that undergo post-prenylation processing follow an indirect targeting pathway requiring initial endoplasmic reticulum membrane association prior to specific organelle targeting...

..Together with the high levels of cathepsin D in immature melanosomes of the RPE, our results suggest that melanin deposition may protect the maturing melanosome from the activity of lumenal acid hydrolases...

..Our results indicate promiscuity in Rab GEF action and suggest that members of related but functionally distinct Rab subfamilies can be controlled by common activators...

..Thus, membrane nanotubes between macrophages are more complex than unvarying ubiquitous membrane tethers and facilitate several means for distal interactions between immune cells...

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..The morphology and function of platelet alpha-granules were unaffected. Our data suggest that Rab27b is a key regulator of dense granule secretion in platelets and thus a candidate gene for delta-storage pool deficiency in humans...

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..The postprenylation events, including the specific targeting of Rabs to target membranes and the requirement for single versus double geranylgeranylation by different Rabs, remain obscure and should be the subject of future studies...

..These data both uncover a major pathogenic factor for RRS and indicate that misfolding of secretory proteins is likely to significantly contribute to human disease and morbidity...

..Our data suggest that Rab27b is functionally redundant with Rab27a and that the pathogenesis of GS is determined by the relative expression of Rab27a and Rab27b in specialized cell types...

..Adenovirus-mediated delivery of REP-1 rescued the defective cells as assessed through protein and enzymatic assays. Ultimately, it may be possible to use virus-mediated delivery of REP-1 to evaluate disease intervention in vivo...

..These results establish a role for Rab27 in platelet synthesis and suggest that Rab27b in particular may coordinate proplatelet formation with granule transport, possibly by recruiting specific effector pathways...

..We conclude that a lumenal cargo protein drives the recruitment of Rab27a to the organelle membrane by a novel mechanism that is indirect, maturation-dependent and cell-type independent...

..We suggest that the restricted phenotypes observed in these diseases result from multiple contributing factors...

..The present strategy represents one way in which the complex pattern of expression and function of proteins involved in specialized cell types may be unraveled...

..Rab27a and myosin VIIa are likely to be required for association with and movement through the apical actin cytoskeleton, which is a prerequisite for entry into the apical processes...

..The diversity of cellular processes regulated by Rab family members is made possible, not only by the wide range of effectors they recruit, but also by the different mechanisms regulating their own targeting and activation...

..These results support the hypothesis that Rabs bind REP via conserved RabF motifs and provide a molecular explanation for the preferential recognition of the GDP-bound conformation of Rab by REP...

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..In conclusion, we present evidence that JFC1 differentially regulates the secretion of PSAP and PSA, and that Rab27a and PI3K play a central role in the exocytosis of prostate-specific markers...