title: The NCLX-type Na+/Ca2+Exchanger NCX-9 Is Required for Patterning of Neural Circuits inCaenorhabditis elegans.
abstract: NCLX is a Na+/Ca2+exchanger that uses energy stored in the transmembrane sodium gradient to facilitate the exchange of sodium ions for ionic calcium. Mammals have a single NCLX, which has been shown to function primarily at the mitochondrion and is an important regulator of neuronal physiology by contributing to neurotransmission and synaptic plasticity. The role of NCLX in developmental cell patterning (e.g.in neural circuits) is largely unknown. Here we describe a novel role for theCaenorhabditis elegansNCLX-type protein, NCX-9, in neural circuit formation. NCX-9 functions in hypodermal seam cells that secrete the axon guidance cue UNC-129/BMP, and our data revealed thatncx-9-/-mutant animals exhibit development defects in stereotyped left/right axon guidance choices within the GABAergic motor neuron circuit. Our data also implicate NCX-9 in a LON-2/heparan sulfate and UNC-6/netrin-mediated, RAC-dependent signaling pathway to guide left/right patterning within this circuit. Finally, we also providein vitrophysiology data supporting the role for NCX-9 in handling calcium exchange at the mitochondrion. Taken together, our work reveals the specificity by which the handling by NCLX of calcium exchange can map to neural circuit patterning and axon guidance decisions during development.
authors.affiliation: From the Department of Biological Sciences and.|the Institute for Neuroscience, George Washington University, Washington, D. C. 20052 and.
authors.forename: Vishal
authors.initials: V
authors.lastname: Sharma
authors.affiliation: the Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8499000, Israel.
authors.forename: Soumitra
authors.initials: S
authors.lastname: Roy
authors.affiliation: the Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8499000, Israel.
authors.forename: Israel
authors.identifier: http://orcid.org/0000-0002-7550-1550
authors.initials: I
authors.lastname: Sekler
authors.affiliation: From the Department of Biological Sciences and damienoh@gwu.edu.|the Institute for Neuroscience, George Washington University, Washington, D. C. 20052 and.
authors.forename: Damien M
authors.identifier: http://orcid.org/0000-0001-5752-2131
authors.initials: DM
authors.lastname: O'Halloran
mesh_terms: D000818:Animals; D000071437:Axon Guidance / Q000502:physiology*; D019521:Body Patterning / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D015398:Signal Transduction; D019831:Sodium-Calcium Exchanger / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D019831:Sodium-Calcium Exchanger; D016212:Transforming Growth Factor beta; C113622:UNC-129 protein, C elegans; D002118:Calcium
keywords: Caenorhabditis elegans (C. elegans); exchanger; mitochondria; sodium-calcium exchange; transporter