James Casanova

..Here we tested the hypothesis that ARF-guanine nucleotide exchange factors (ARF-GEFs) of the cytohesin/ARNO family mediate the activation of ARF and PLD by insulin...

..In this themes article, I review current hypotheses about how these processes are integrated and attempt to identify fruitful areas for future research...

..Here we review recent progress in our understanding of the structure, localization and biology of the different classes of Arf GEFs...

..These observations suggest that, in addition to its role in endocytic regulation at the plasma membrane, BRAG2 also functions within the nucleus...

..However, mutant SCAMP2 also uniquely inhibits fusion pore dilation. Thus, SCAMP2 couples Arf6-stimulated PLD activity to exocytosis and links this process to formation of fusion pores...

..Although infection leads to the formation of an IRSp53/WAVE2 complex, it is the association of WAVE2 with the Abi1/Nap1/PIR121/HSPC300 complex that regulates bacterial internalization...

..These findings suggest that Arf6 regulates both endocytosis and recycling of beta1 integrins and that BRAG2 functions selectively to activate Arf6 during integrin internalization...

..enterica serovar Typhimurium SopE are individually required for basolateral internalization. These results underscore that the specific factors required for Salmonella invasion differ between membrane domains of polarized epithelia...

..The addition of platelet-derived growth factor (PDGF) to fibroblasts triggered a rapid and transient increase in FRET, indicative of Arf6 activation. These reagents should be useful for investigations of Arf6 activation and function...

..Together, these data suggest that ARNO and ARF6 coordinate with the Dock180/Elmo complex to promote Rac activation at the leading edge of migrating cells...

..Here, we review recent progress in our understanding of how Arfs and their interacting proteins function to integrate membrane and cytoskeletal dynamics...

..Because PTB-domain-containing adaptor proteins influence endocytosis and trafficking of membrane proteins and cell migration [15, 16], our data support a model wherein PTB-domain-containing adaptor proteins regulate Arf family proteins...

..Finally, we found that expression of AGAP1 induces a surprising reciprocal activation of Arf6, which suggests that regulatory cross talk exists among Arf isoforms...

..Both of these steps are required for the plasma membrane targeting of Rac1 and for its activation. These data therefore define a new membrane raft trafficking pathway that is crucial for anchorage-dependent signalling...

..This review is intended to summarize our current understanding of the tools used by Salmonella to enter host cells, with a focus on effectors that modulate the actin cytoskeleton...

..Taken together, these findings indicate that c-Abl is activated during S. enterica serovar Typhimurium infection and that its phosphorylation of multiple downstream targets is functionally important in bacterial internalization...

..Together, these findings reveal a novel role for focal adhesion proteins in the invasion of host cells by Salmonella...

..Recent studies have identified a family of GTPase activating proteins (GAPs) that contain both ARF-GAP and Rho-GAP domains, providing the first direct link between these two signaling pathways...

..We conclude that ARAP2 is an Arf6GAP that functions downstream of RhoA to regulate focal adhesion dynamics...

..These studies identify TRE17 as a novel regulator of the Arf6-regulated plasma membrane recycling system and reveal an unexpected function for TBC domains...

..We also demonstrate the utility of using Salmonella invasion as a model of endosomal recycling events...

..We conclude that ARNO acts together with ARF6 to regulate apical endocytosis...

..These results suggest that ARNO and ARF6, through PI(4)P 5-Kinase alpha, regulate axonal elongation and branching during neuronal development...

..We hypothesize that ARF6 might also serve GPCRs other than the LH/CG R to regulate the availability of arrestin 2 for receptor desensitization...

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..These data suggest that Rab14 specifically regulates delivery of cargo from the TGN to the apical domain...

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..These hypotheses will be tested in specifc Aim 3. The overall goal of the proposed research is to determine the mechanisms by which Salmonella enter host intestinal cells and cause disease. ..

..These hypotheses will be tested in specifc Aim 3. The overall goal of the proposed research is to determine the mechanisms by which Salmonella enter host intestinal cells and cause disease. ..

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..These studies will provide insight into the mechanisms by which macromolecules are transported across epithelia, a process that is particularly important in the mucosal immunity. ..

..The results of these studies will provide significant insight into the mechanisms of Salmonella pathogenesis within the intestinal epithelium. ..

..The goals of this research are to define the host cell machinery that is subverted by Salmonella to enter the intestinal epithelium and spread systemically, and to characterize the innate immune responses to Salmonella infection. ..