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doi: 10.1242/10.1242/jcs.00072

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Neuronal calcium sensor 1 and phosphatidylinositol 4-OH kinase ß interact in neuronal cells and are translocated to membranes during nucleotide-evoked exocytosis

¹ CNR, Institute of Neuroscience, Cellular and Molecular Pharmacology, Center of Excellence on Neurodegenerative Diseases, Department of Medical Pharmacology, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy
² Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada M5G 1X5
³ School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK

^* Author for correspondence (e-mail: p.rosa{at}csfic.mi.cnr.it)

Accepted 29 July 2002

Neuronal calcium sensor 1 (NCS-1) belongs to a family of EF-hand calcium-binding proteins and is mainly expressed in neurons and neuroendocrine cells, where it causes facilitation of neurotransmitter release through unknown mechanisms. The yeast homologue of NCS-1 has been demonstrated to interact with and regulate the activity of yeast phosphatidylinositol 4-OH kinase ß (PI4Kß). However, in neurons and neurosecretory cells NCS-1 has not unequivocally been shown to interact with PI4Kß. Here we have compared the subcellular distribution of NCS-1 and PI4Kß and investigated whether they are capable of forming complexes. In neurons, both proteins are widely distributed and are present in perikarya and, to a lesser extent, in nerve terminals. A consistent portion of NCS-1 and PIK4ß is cytosolic, whereas a portion of both proteins appears to be associated with the membranes of the endoplasmic reticulum and the Golgi complex. Very small amounts of NCS-1 and PI4Kß are present in synaptic vesicles. Our results further demonstrate that in neurosecretory cells, endogenous NCS-1 and PIK4ß interact to form a complex that can be immunoisolated from membrane as well as from cytosolic fractions. Moreover, both proteins can be recruited to membranes when cells are treated with nucleotide receptor agonists known to increase polyphosphoinositide turnover and concomitantly induce exocytosis of secretory vesicles. Finally, in PC12 cells overexpressing NCS-1, the amount of PI4Kß associated with the membranes is increased concomitantly with the increased levels of NCS-1 detected in the same membrane fractions. Together, these findings demonstrate that mammalian NCS-1 and PI4Kß interact under physiological conditions, which suggest a possible role for NCS-1 in the translocation of PI4Kß to target membranes.

Key words: Calcium-binding proteins, Neuronal calcium sensor 1, Phosphatidylinositol 4-OH kinase, Polyphosphoinositides, Membrane traffic

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