The NCLX-type Na + /Ca 2+ exchanger NCX-9 is required for patterning of neural circuits in Caenorhabditis elegans

Vishal Sharma, Soumitra Roy, Israel Sekler, Damien M. O'Halloran

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


NCLX is a Na + /Ca 2+ 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 the Caenorhabditis elegans NCLX-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 that ncx-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 provide in vitro physiology 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.

Original languageEnglish
Pages (from-to)5364-5377
Number of pages14
JournalJournal of Biological Chemistry
Issue number13
StatePublished - 31 Mar 2017

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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