Physiological roles of Rab27 effectors in regulated exocytosis.
Recent discoveries that Rab27a/b and their multiple effectors are involved in the regulated exocytosis of lysosome-related organelles and secretory granules have generated numerous related studies. However, not all of these studies have yielded physiologically relevant data because they were not all performed under physiological conditions. For example, "in vivo interactions" have been claimed without examination of the endogenous complex. In some studies, the only proof of interaction was between exogenously expressed proteins in cultured cells where these proteins are not normally expressed. Because regulated exocytic pathways contain highly differentiated secretory organelles, it is important to analyze the molecular interaction in cells harboring these organelles and the associated molecules. Furthermore, previous overexpression experiments to examine the effect on secretion often failed to compare the level of the exogenous protein with that of the endogenous one. Similarly, some knockdown experiments using small-interfering RNAs have only shown downregulation of the exogenously expressed protein, and not of the endogenous one. Many of the conflicting findings in previous studies may be attributable to these shortcomings. The present study summarizes our knowledge about the roles of Rab27 effectors in regulated exocytic pathways based on physiologically relevant data.
Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University.
Tetsuro
T
Izumi
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D005089:Exocytosis / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D005810:Multigene Family / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D033921:Vesicular Transport Proteins / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000502:physiology*; D000075745:rab27 GTP-Binding Proteins
D048868:Adaptor Proteins, Signal Transducing; C492410:MLPH protein, human; C501262:MYRIP protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C120704:RPH3AL protein, human; C431146:SYTL1 protein, human; C512779:SYTL4 protein, human; C424134:Sytl2 protein, mouse; C507969:UNC13D protein, human; D033921:Vesicular Transport Proteins; D000075745:rab27 GTP-Binding Proteins; C519993:rabphilin protein, mouse; C066694:RAB27A protein, human; C512960:Rab27B protein, human; D020691:rab GTP-Binding Proteins