title: Interaction of neuronal calcium sensor-1 and ADP-ribosylation factor 1 allows bidirectional control of phosphatidylinositol 4-kinase beta and trans-Golgi network-plasma membrane traffic.
abstract: We have identified a novel Ca(2+)-dependent interaction between neuronal calcium sensor-1 (NCS-1) and the GTPase ARF1. Both of these proteins are localized to the Golgi complex, and both regulate phosphatidylinositol 4-kinase IIIbeta (PI(4)Kbeta). Spatial and temporal control of phosphatidylinositol 4-phosphate levels through activation of PI(4)Kbeta is important for the recruitment of trafficking complexes to the trans-Golgi network (TGN) and vesicular traffic from this organelle. The NCS-1-ARF1 interaction and its specificity have been demonstrated through in vitro binding assays, in vitro enzyme assay, and through functional cellular assays. We show that NCS-1 can exert bidirectional effects to activate PI(4)Kbeta on its own or inhibit the activation by ARF1. NCS-1 was shown to modulate the effects of expression of ARF mutants that disrupt Golgi morphology and to recruit GDP-loaded ARF to the Golgi complex in a Ca(2+)-dependent manner. We demonstrate antagonist effects of NCS-1 and ARF on constitutive and regulated exocytosis. The NCS-1-ARF1 interaction provides evidence for functional cross-talk between Ca(2+)-dependent and ARF-dependent pathways in TGN to plasma membrane traffic.
authors.affiliation: Physiological Laboratory, School of Biomedical Sciences, University of Liverpool, Crown St., Liverpool L69 3BX, UK.
authors.forename: Lee P
authors.initials: LP
authors.lastname: Haynes
authors.forename: Geraint M H
authors.initials: GM
authors.lastname: Thomas
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burgoyne
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000235:genetics / Q000378:metabolism*; D020823:ADP-Ribosylation Factor 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism*; D004789:Enzyme Activation; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D010641:Phenotype; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport; D051381:Rats; D013379:Substrate Specificity; D014759:Viral Envelope Proteins / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D014759:Viral Envelope Proteins; C101464:frequenin calcium sensor proteins; D019382:Human Growth Hormone; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D019870:1-Phosphatidylinositol 4-Kinase; D020823:ADP-Ribosylation Factor 1; D002118:Calcium