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In the current study, clients of male escorts answered questions about sexual behavior with their last hire. Latent class analysis identified four client sets based on these variables. Clients reporting condomless anal sex were in the minority Escorts who engage in anal sex with clients might be appropriate to train in HIV prevention and other harm reduction practices-adopting the perspective of "sex workers as sex educators. Defects in membrane trafficking are hallmarks of neurodegeneration. Rab GTPases are key regulators of membrane trafficking.

Alterations of Rab GTPases, or the membrane compartments they regulate, are associated with virtually all neuronal activities in health and disease. The observation that many Rab GTPases are associated with neurodegeneration has proven a challenge in the quest for cause and effect. Neurodegeneration can be a direct consequence of a defect in membrane trafficking. Alternatively, changes in membrane trafficking may be secondary consequences or cellular responses.

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The secondary consequences and cellular responses, in turn, may protect, represent inconsequential correlates or function as drivers of pathology. We provide an overview of current knowledge on Rab GTPase functions in neurons and review the associations of Rab GTPases with neurodegeneration with respect to the following classifications: primary cause, secondary cause driving pathology or secondary correlate.

This analysis is devised to aid the interpretation of frequently observed membrane trafficking defects in neurodegeneration and facilitate the identification of true causes of pathology. RAB meetings shall be open to the public.

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The role of the small GTPase Rab 31 in cancer. Members of the small GTPase family Rab are emerging as potentially important factors in cancer development and progression. A good number of Rabs have been implicated or associated with various human cancers, and much recent excitement has been associated with the roles of the Rab 11 subfamily member Rab 25 and its effector, the Rab coupling protein RCP , in tumourigenesis and metastasis. In this review, we focus on a Rab 5 subfamily member, Rab 31, and its implicated role in cancer. Well recognized as a breast cancer marker with good prognostic value, recent findings have provided some insights as to the mechanism underlying Rab 31's influence on oncogenesis.

Elevated Rab 31 stabilizes MUC1-C levels in an auto-inductive loop that could lead to aberrant signalling and gene expression associated with cancer progression. Rab 31 and its guanine nucleotide exchange factor GAPex-5 have, however, also been shown to enhance early endosome-late endosome transport and degradation of the epidermal growth factor receptor EGFR.

The multifaceted action and influences of Rab 31 in cancer is discussed in the light of its new interacting partners and pathways. Bultema, Jarred J. Class V myosins are actin-based motors with conserved functions in vesicle and organelle trafficking.

Herein we report the discovery of a function for Myosin Vc in melanosome biogenesis as an effector of melanosome-associated Rab GTPases. We isolated Myosin Vc in a yeast two-hybrid screening for proteins that interact with Rab 38, a Rab protein involved in the biogenesis of melanosomes and other lysosome-related organelles.

Binding depends on residues in the switch II region of Rab 32 and Rab 38 and regions of the Myosin Vc coiled-coil tail domain. Although Myosin Vc is not particularly abundant on pigmented melanosomes, its knockdown in MNT-1 melanocytes caused defects in the trafficking of integral membrane proteins to melanosomes with substantially increased surface expression of Tyrp1, nearly complete loss of Tyrp2, and significant Vamp7 mislocalization.

Knockdown of Myosin Vc in MNT-1 cells more than doubled the abundance of pigmented melanosomes but did not change the number of unpigmented melanosomes. Together the data demonstrate a novel role for Myosin Vc in melanosome biogenesis and secretion. Myosin vc interacts with Rab 32 and Rab 38 proteins and works in the biogenesis and secretion of melanosomes. Rab proteins constitute the largest subfamily of Ras-like small GTPases. They are central to vesicular transport and organelle definition in eukaryotic cells. Unlike their Ras counterparts, they are not a hallmark of cancer.

However, a number of diseases, including cancer, show a misregulation of Rab protein activity. As for all membrane-anchored signaling proteins, correct membrane organization is critical for Rabs to operate. In this chapter, we provide a detailed protocol for the use of a flow cytometry-based Fluorescence Resonance Energy Transfer FRET -biosensors assay, which allows to detect changes in membrane anchorage, subcellular distribution, and of the nanoscale organization of Rab -GTPases in mammalian cell lines.

This assay is high-throughput amenable and can therefore be utilized in chemical-genomic and drug discovery efforts.

Molecular cloning of Rab 5 Ap Rab 5 in Aiptasia pulchella and its retention in phagosomes harboring live zooxanthellae. The intracellular association of symbiotic dinoflagellates zooxanthellae with marine cnidarians is the very foundation of the highly productive and diversified coral reef ecosystems. To reveal its underlying molecular mechanisms, we previously cloned Ap Rab 7, a Rab 7 homologue of the sea anemone Aiptasia pulchella, and demonstrated its selective exclusion from phagosomes containing live zooxanthellae, but not from those containing either dead or photosynthesis-impaired algae.

In this study, Rab 5 was characterized, due to its key role in endocytosis and phagocytosis acting upstream of Rab 7. The Aiptasia Rab 5 homologue Ap Rab 5 is Subcellular fractionation study showed that Ap Rab 5 is mainly cytosolic. EGFP reporter and phagocytosis studies indicated that membrane-associated Ap Rab 5 is present in early endocytic and phagocytic compartments, and is able to promote their fusion.

Significantly, immunofluorescence study showed that the majority of phagosomes containing either resident or newly internalized live zooxanthellae were labeled with Ap Rab 5, while those containing either heat-killed or photosynthesis-impaired algae were mostly negative for Ap Rab 5 staining whereas the opposite was observed for Ap Rab 7.

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Rab proteins in the brain and corpus allatum of Bombyx mori. In eukaryotic cells, Rab guanosine triphosphate-ases serve as key regulators of membrane-trafficking events, such as exocytosis and endocytosis. Rab 3, Rab 6, and Rab 27 control the regulatory secretory pathway of neuropeptides and neurotransmitters. We then produced antibodies against Rab 3, Rab 6, and Rab 27 of Bombyx mori in rabbits and rats for use in western immunoblotting and immunohistochemistry.

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Immunohistochemistry results revealed that Rab 3, Rab 6, and Rab 27 expression was restricted to neurons in the pars intercerebralis and dorsolateral protocerebrum of the brain. Rab 3 and Rab 6 co-localized with bombyxin, an insect neuropeptide. However, there was no Rab that co-localized with prothoracicotropic hormone. The corpus allatum secretes neuropeptides synthesized in the brain into the hemolymph. Results showed that Rab 3 and Rab 6 co-localized with bombyxin in the corpus allatum.

These findings suggest that Rab 3 and Rab 6 are involved in neurosecretion in B. This study is the first to report a possible relationship between Rab and neurosecretion in the insect corpus allatum. The C. Rab monomeric GTPases regulate specific aspects of vesicle transport in eukaryotes including coat recruitment, uncoating, fission, motility, target selection and fusion.

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Moreover, individual Rab proteins function at specific sites within the cell, for example the ER, golgi and early endosome. Importantly, the localization and function of individual Rab subfamily members are often conserved underscoring the significant contributions that model organisms such as Caenorhabditis elegans can make towards a better understanding of human disease caused by Rab and vesicle trafficking malfunction.

With this in mind, a bioinformatics approach was first taken to identify and classify the complete C. For genes that were difficult to classify by sequence similarity alone, we did a comparative analysis of intron position among specific subfamilies from yeast to humans. This two-pronged approach allowed the classification of 30 out of 31 C.

Second, a molecular toolset was created to facilitate research on biological processes that involve Rab proteins. Specifically, we used Gateway-compatible C. Rab 1a regulates sorting of early endocytic vesicles. We previously reported that Rab 1a is associated with asialoorosomucoid ASOR -containing early endocytic vesicles, where it is required for their microtubule-based motility. In Rab 1a knockdown KD cell lines, ASOR failed to segregate from its receptor and, consequently, did not reach lysosomes for degradation, indicating a defect in early endosome sorting.

The present study shows that Rab 1a has a more general role in endocytic vesicle processing that extends to EGF and transferrin Tfn trafficking. Compared with results in control Huh7 cells, EGF accumulated in aggregates within Rab 1a KD cells, failing to reach lysosomal compartments. Tfn, a prototypical example of recycling cargo, accumulated in a Rab mediated slow-recycling compartment in Rab 1a KD cells, in contrast to control cells, which sort Tfn into a fast-recycling Rab 4 compartment. These data indicate that Rab 1a is an important regulator of early endosome sorting for multiple cargo species.

The effectors and accessory proteins recruited by Rab 1a to early endocytic vesicles include the minus-end-directed kinesin motor KifC1, while others remain to be discovered. Rab 2 promotes autophagic and endocytic lysosomal degradation.

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Rab 7 promotes fusion of autophagosomes and late endosomes with lysosomes in yeast and metazoan cells, acting together with its effector, the tethering complex HOPS. Here we show that another small GTPase, Rab 2, is also required for autophagosome and endosome maturation and proper lysosome function in Drosophila melanogaster. Importantly, expression of active Rab 2 promotes autolysosomal fusions unlike that of GTP-locked Rab 7, suggesting that its amount is normally rate limiting. We also demonstrate that RAB 2A is required for autophagosome clearance in human breast cancer cells.

In conclusion, we identify Rab 2 as a key factor for autophagic and endocytic cargo delivery to and degradation in lysosomes. Endosomal membrane trafficking requires coordination between phosphoinositide lipids, Rab GTPases, and microtubule-based motors to dynamically determine endosome identity and promote long-range organelle transport. AnkB associates with phosphatidylinositol 3-phosphate PI3P -positive organelles in fibroblasts and binds dynactin to promote their long-range motility.

Taken together our results indicate that RAB and AMPH-1 mediated down-regulation of RAB -5 is an important step in recycling, required for cargo exit from early endosomes and regulation of early endosome—recycling endosome interactions. Identification and characterization of a member of Rab subfamily, Rab 8, from Clonorchis sinensis. It regulates a broad spectrum of cellular processes including cell proliferation, cytoskeletal assembly, and intracellular membrane trafficking in eukaryotes.

The Rab 8 from Clonorchis sinensis Cs Rab 8 was composed of amino acids. A phylogenic tree analysis indicated that the Cs Rab 8 was clustered with the Rab from Schistosoma japonicum, and trematode and tapeworm came from the same branch, which was different from an evolutional branch built by other species, such as mammal animal, insecta, nematode, and reptile. The transcriptional level of Cs Rab 8 at metacercaria stage was the highest at the four stages and higher by Immunohistochemical localization analysis showed that Cs Rab 8 was specifically distributed in the tegument, vitellarium, eggs, and testicle of adult worms, and detected on the vitellarium and tegument of metacercaria.

Combined with the results, Cs Rab 8 is indispensable for survival and development of parasites, especially for regulating.


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The Drosophila nephrocyte is a critical component of the fly renal system and bears structural and functional homology to podocytes and proximal tubule cells of the mammalian kidney. Investigations of nephrocyte cell biological processes are fundamental to understanding the insect renal system.

Nephrocytes are highly active in endocytosis and vesicle trafficking. Rab GTPases regulate endocytosis and trafficking but specific functions of nephrocyte Rabs remain undefined. We analyzed Rab GTPase expression and function in Drosophila nephrocytes and found that 11 out of 27 Drosophila Rabs were required for normal activity.

Rabs 1, 5, 7, 11 and 35 were most important. Gene silencing of the nephrocyte-specific Rab 5 eliminated all intracellular vesicles and the specialized plasma membrane structures essential for nephrocyte function. Rab 7 silencing dramatically increased clear vacuoles and reduced lysosomes. Rab 11 silencing increased lysosomes and reduced clear vacuoles. Our results suggest that Rab 5 mediates endocytosis that is essential for the maintenance of functionally critical nephrocyte plasma membrane structures and that Rabs 7 and 11 mediate alternative downstream vesicle trafficking pathways leading to protein degradation and membrane recycling, respectively.

Elucidating molecular pathways underlying nephrocyte function has the potential to yield important insights into human kidney cell physiology and mechanisms of cell injury that lead to disease. The Drosophila nephrocyte is emerging as a useful in vivo model system for molecular target identification and initial testing of therapeutic approaches in humans.

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After endocytosis, membrane proteins are often sorted between two alternative pathways: a recycling pathway and a degradation pathway. Relatively little is known about how trafficking through these alternative pathways is differentially regulated. In coelomocytes, postendocytic trafficking of the marker Texas Red-bovine serum albumin was delayed. These results define a new function for Rab 2 in protein trafficking.

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