Syndapin 3 modulates fusion pore expansion in mouse neuroendocrine chromaffin cells.
Adrenal neuroendocrine chromaffin cells receive excitatory synaptic input from the sympathetic nervous system and secrete hormones into the peripheral circulation. Under basal sympathetic tone, modest amounts of freely soluble catecholamine are selectively released through a restricted fusion pore formed between the secretory granule and the plasma membrane. Upon activation of the sympathoadrenal stress reflex, elevated stimulation drives fusion pore expansion, resulting in increased catecholamine secretion and facilitating release of copackaged peptide hormones. Thus regulated expansion of the secretory fusion pore is a control point for differential hormone release of the sympathoadrenal stress response. Previous work has shown that syndapin 1 deletion alters transmitter release and that the dynamin 1-syndapin 1 interaction is necessary for coupled endocytosis in neurons. Dynamin has also been shown to be involved in regulation of fusion pore expansion in neuroendocrine chromaffin cells through an activity-dependent association with syndapin. However, it is not known which syndapin isoform(s) contributes to pore dynamics in neuroendocrine cells. Nor is it known at what stage of the secretion process dynamin and syndapin associate to modulate pore expansion. Here we investigate the expression and localization of syndapin isoforms and determine which are involved in mediating fusion pore expansion. We show that all syndapin isoforms are expressed in the adrenal medulla. Mutation of the SH3 dynamin-binding domain of all syndapin isoforms shows that fusion pore expansion and catecholamine release are limited specifically by mutation of syndapin 3. The mutation also disrupts targeting of syndapin 3 to the cell periphery. Syndapin 3 exists in a persistent colocalized state with dynamin 1.
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio; and.
Prattana
P
Samasilp
Kyle
K
Lopin
Shyue-An
SA
Chan
Rajesh
R
Ramachandran
Corey
C
Smith
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D034284:Dynamin I / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008561:Membrane Fusion; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009479:Neuropeptides / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D016062:Porosity; D011485:Protein Binding; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014162:Transfection; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D002395:Catecholamines; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; C492182:PACSIN1 protein, human; C421762:PACSIN3 protein, human; C114726:Pacsin1 protein, mouse; C485644:Pacsin2 protein, mouse; C492181:Pacsin2 protein, rat; C486019:Pacsin3 protein, mouse; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; D034284:Dynamin I
catecholamine; chromaffin cells; fusion pore; neuroendocrine; syndapin