2007
DOI: 10.1152/ajpgi.00388.2006
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Synaptotagmin I binds intestinal epithelial NHE3 and mediates cAMP- and Ca2+-induced endocytosis by recruitment of AP2 and clathrin

Abstract: Apical membrane sodium hydrogen exchanger 3 (NHE3), a major pathway for non-nutrient-dependent intestinal Na(+) absorption, is tightly regulated by second messenger systems that affect its functional activity and membrane trafficking. However, the events and components involved in NHE3 regulation are only partially understood. We report that the adaptor protein synaptotagmin I (Syt I) plays a pivotal role in cAMP- and Ca(2+)-induced cargo recognition of NHE3 and initiation of its endocytosis. Both mouse small … Show more

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Cited by 31 publications
(43 citation statements)
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“…Second messenger-induced DRA endocytosis is dependent on association with the adaptor protein Syt I with subsequent recruitment of AP2 and clathrin. The process therefore appears to be common with that observed for apical NHEs (34).…”
Section: Discussionsupporting
confidence: 67%
See 2 more Smart Citations
“…Second messenger-induced DRA endocytosis is dependent on association with the adaptor protein Syt I with subsequent recruitment of AP2 and clathrin. The process therefore appears to be common with that observed for apical NHEs (34).…”
Section: Discussionsupporting
confidence: 67%
“…To determine whether DRA activity is regulated by second messenger cAMP or intracellular calcium, we treated DRA transgene-infected Caco2BBE monolayers with either the permeable 8-CPT-cAMP (100 M, 15 min) or the Ca 2ϩ -ATPase inhibitor thapsigargin (100 ng/ml, 15 min) to increase intracellular free Ca 2ϩ . These agents inhibit a large percentage of the apical Na ϩ influx mediated by NHE2 and NHE3 (34). Both of these second messenger pathway regulators also inhibited DRA activity (Fig.…”
Section: Infection With Virus Containing Dra Increases Apical Namentioning
confidence: 80%
See 1 more Smart Citation
“…Basal microvillus NHE3 was increased by myosin VI KD, whereas the secondmessenger-induced (FSH and CCH) decrease in microvillus NHE3 activity and amount was blocked. Because these two agents have been shown to stimulate endocytosis without altering the rates of exocytosis (Gekle et al, 2002;Lee-Kwon et al, 2003;Musch et al, 2007;Zachos et al, 2013), we propose that both basal and stimulated endocytosis require myosin VI. Additionally, because EGF treatment of myosin VI KD cells still led to an increase in microvillar NHE3 activity, our results further indicate that myosin VI is not involved in the stimulated exocytosis of NHE3 in the Na + -absorptive cell.…”
Section: Discussionmentioning
confidence: 93%
“…Depletion of either synaptotagmin 1 or 2 resulted in increased sphingomyelin trafficking to the inclusion. Synaptotagmins are calcium binding proteins that are best known for their role in vesicular trafficking at synapses but are also expressed in nonsynaptic cells (40,43). Synaptotagmins have extensive roles in cellular signaling pathways, including regulating exocytic vesicles from the Golgi apparatus (57) and binding the MVB marker CD63 (18); both pathways are implicated in sphingomyelin trafficking to the inclusion (5,22,48).…”
Section: Vol 79 2011mentioning
confidence: 99%