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The role of ArfGAP1 as a terminator or effector in COPI-vesicle formation has been the subject of ongoing discussions. Here, the discussion on the putative terminator/effector functions has been enlarged to include Arf GAP members involved in the formation of clathrin-coated vesicles. ACAP1, whose role has been studied extensively, enhances the recycling of endocytosed proteins to the plasma membrane. Importantly, this positive role appears to be an overall reflection of both the terminator and effector activities attributed to ACAP1. Other Arf GAP subtypes have also been suggested to possess both terminator and effector activities. Interestingly, while most Arf GAP proteins regulate membrane trafficking by acting as facilitators, a few Arf GAP subtypes act as inhibitors.
Dr. Nava Segev weighs in on the Arf GAP debate covered in reviews published in Cellular Logistics volume 1, issue 2.
Read more at: http://www.landesbioscience.com/journals/cellularlogistics/article/15738
Studies from our group suggest that ARFGAP1 acts not only as an ARF regulator but also as an ARF effector, with both roles promoting COPI vesicle formation. However, others have concluded differently, specifically that ARFGAP1 only acts as an ARF regulator, which involves inhibition of COPI vesicle formation by preventing components of the COPI complex from binding to target membrane. Here, we propose plausible reconciling explanations for this apparent contradiction.
Download the full-text article at: http://www.landesbioscience.com/journals/cellularlogistics/article/15175/
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Trafficking in the early secretory pathway at first glance is well understood according to textbook knowledge: To achieve secretion and to maintain organelle homeostasis, protein and lipid cargo need to be transported constitutively from their origins of biosynthesis to their respective destinations. Thus, secretory cargo exits the ER and is shuttled to the Golgi via vesicular COPII carriers. Lipid and protein cargo is enzymatically modified in the Golgi, transported from cis- to trans- (by mechanisms that are still debated today), and from there travel to their final destinations. The best established roles for COPI vesicles, simply spoken, is to mediate retrograde trafficking of cargo molecules that were transported forward, but need to be transported back.
Download the full-text article at: http://www.landesbioscience.com/journals/cellularlogistics/article/15174/
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Whether your passion is to understand and reverse disease processes or “simply” a better understanding of how cells work, anyone wishing to understand cell regulation today must have a detailed and accurate understanding of regulatory GTPase mechanisms and their application to specific pathways. This is becoming increasingly difficult as the details of signaling by members of different families of GTPases and their regulators expand. But this is all the more reason to continually ask, which aspects of GTPase signaling are distinct to a GTPase or its subfamily and which are conserved throughout the superfamily? We each have slightly different views of the key aspects of GTPase signaling that are derived from the main GTPases studied in our own labs; e.g., translocation onto a membrane is an essential and integral aspect of Arf activation but not of other GTPases. However, one aspect of GTPase signaling that I had come to believe to be widespread and of general importance is not universally accepted. In fact, through my conversations at the recent FASEB summer research conference on “Arf Family GTPases” and reading of the literature in a graduate tutorial class, I realized that it is not known or accepted by the majority of researchers. The question is the role of GTPase activating proteins (GAPs) in signaling. Are they “pure” terminators of signaling or do they serve effector functions?
Read more at: http://www.landesbioscience.com/journals/cellularlogistics/article/15153
To see Dr. Kahn's recent review "Models for the functions of Arf GAPs" in Seminars in Cell & Developmental Biology21 mentioned in this review, click [here] (Link leads to Elsevier's website).
This entry is related to an Editorial from our first issue, introducing the CellLogBlog to our readers.
http://www.landesbioscience.com/journals/cellularlogistics/article/14331
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