title: Neuronal Ca2+ sensor protein VILIP-1 affects cGMP signalling of guanylyl cyclase B by regulating clathrin-dependent receptor recycling in hippocampal neurons.
abstract: The family of neuronal Ca2+ sensor (NCS) proteins is known to influence a variety of physiological and pathological processes by affecting signalling of different receptors and ion channels. Recently, it has been shown that the NCS protein VILIP-1 influences the activity of the receptor guanylyl cyclase GC-B. In transfected cell lines, VILIP-1 performs a Ca2+-dependent membrane association, the reversible Ca2+-myristoyl switch of VILIP-1, which leads to an increase in natriuretic peptide-stimulated cGMP levels. In this study, we have investigated the effect of VILIP-1 on cGMP signalling in C6 cells and in primary hippocampal neurons, where VILIP-1 and GC-B are co-expressed in many but not all neurons and partially co-localize in the soma and in dendrites. Our data indicate that VILIP-1 modulates GC-B activity by influencing clathrin-dependent receptor recycling. These data support a general physiological role for VILIP-1 in membrane trafficking in the intact hippocampus, where the NCS protein may affect processes, such as neuronal differentiation and synaptic plasticity e.g. by influencing cGMP-signalling.
authors.affiliation: Signal Transduction Research Group, Charité, University Medicine, 10117 Berlin, Germany.
authors.forename: Marian
authors.initials: M
authors.lastname: Brackmann
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schuchmann
authors.forename: Rene
authors.initials: R
authors.lastname: Anand
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Braunewell
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002966:Clathrin / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D051596:Neurocalcin; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D000099242:Atrial Natriuretic Factor Receptor B
chemical_list: D002966:Clathrin; D006152:Cyclic GMP; D006162:Guanylate Cyclase; D009419:Nerve Tissue Proteins; D051596:Neurocalcin; D017461:Receptors, Atrial Natriuretic Factor; D044169:Receptors, Calcium-Sensing; D000099242:Atrial Natriuretic Factor Receptor B; C496690:Vsnl1 protein, rat