Neuronal calcium sensor-1 (NCS-1) or the originally identified homologue frequenin belongs to a superfamily of EF-hand calcium binding proteins. Although NCS-1 is thought to enhance synaptic efficacy or exocytosis mainly by activating ion channel function, the detailed molecular basis for the enhancement is still a matter of debate. Here, mechanisms underlying the NCS-1-evoked enhancement of exocytosis were investigated using PC12 cells overexpressing NCS-1. NCS-1 was found to have a broad distribution in the cells being partially distributed in the cytosol and associated to vesicles and tubular-like structures. Biochemical and immunohistochemical studies indicated that NCS-1 partially colocalized with the light synaptic vesicle marker synaptophysin. When stimulated with UTP or bradykinin, agonists to phospholipase C-linked receptors, NCS-1 enhanced the agonist-mediated elementary and global Ca2+ signaling and increased the levels of downstream signals of phosphatidylinositol 4-kinase. NCS-1 enhanced the UTP-evoked exocytosis but not the depolarization-evoked Ca2+ responses or exocytosis, suggesting that the enhancement by NCS-1 should involve phospholipase C-linked receptor-mediated signals rather than the Ca2+ channels or exocytotic machinery per se. Taken together, NCS-1 enhances phosphoinositide turnover, resulting in enhancement of Ca2+ signaling and exocytosis. This is a novel regulatory mechanism of exocytosis that might involve the activation of phosphatidylinositol 4-kinase.
Mechanisms underlying the neuronal calcium sensor-1-evoked enhancement of exocytosis in PC12 cells / S. Koizumi, P. Rosa, G.B. Willars, R.A.J. Challiss, E. Taverna, M. Francolini, M.D. Bootman, P. Lipp, K. Inoue, J. Roder, A. Jeromin. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 277:33(2002 Aug 16), pp. 30315-30324.
|Titolo:||Mechanisms underlying the neuronal calcium sensor-1-evoked enhancement of exocytosis in PC12 cells|
|Parole Chiave:||Animals ; Uridine Triphosphate ; Calcium ; Bradykinin ; Phosphatidylinositols ; Exocytosis ; Subcellular Fractions ; Potassium ; Rats ; Calcium-Binding Proteins ; Fluorescent Antibody Technique ; Neuropeptides ; Signal Transduction ; Neuronal Calcium-Sensor Proteins ; PC12 Cells|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||16-ago-2002|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1074/jbc.M201132200|
|Appare nelle tipologie:||01 - Articolo su periodico|