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. 2005 Feb 18;280(7):6047-54.
doi: 10.1074/jbc.M413090200. Epub 2004 Dec 2.

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

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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

Lee P Haynes et al. J Biol Chem. .
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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.

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