Comparative Analysis of the Sodium-Calcium Exchanger Superfamily
Open Access DepositedNa+/Ca2+ exchangers are low affinity/high-capacity transporters that mediate Ca2+ extrusion by coupling Ca2+ efflux to the influx of Na+ ions. Their primary function is to maintain Ca2+ homeostasis in cells of all organisms and they play a particularly important role in excitable cells that experience transient Ca2+ fluxes. While their functions have been studied extensively in muscle cells, much is still unknown about their contributions to the nervous system. Data suggests that Na+/Ca2+ exchangers play a key role in neuronal processes such as memory formation, learning, oligodendrocyte differentiation and axon guidance. They are also implicated in pathologies such as Alzheimer’s Disease, Parkinson’s Disease, Multiple Sclerosis and Epilepsy. While they are implicated in critical neuronal processes, a clear understanding of their mechanism remains unknown. In order to facilitate the exchange of data from many different branches of biology and to further the research in the field of sodium calcium exchangers, this dissertation presents the first centralized database of sodium calcium exchangers called NCX-DB, which provides a platform and suite tools for researchers to compare exchangers across species while also discovering and characterizing new exchangers. This dissertation examines the differences in sodium calcium exchanger counts across species from the Phylum Nematoda and details expansions and contractions of specific exchanger subtypes within certain nematode clades. Data presented here provides evidence for a role of sodium calcium exchangers in the activation of the infective larval stage of parasites by examining differentially expressed genes in non-activated versus activated infective stage larvae. Findings presented in this dissertation point to a heterogenous picture of sodium calcium exchanger evolution across the Phylum Nematoda that may reflect unique adaptations to free-living and parasitic lifestyles. Furthermore, this dissertation characterizes the two NCLX type sodium calcium exchanger genes, ncx-6 and ncx-7, in Caenorhabditis elegans. Both are expressed in the ADL head sensory neurons in addition to the intestine. Results show that both exchangers are needed for the aversive response behavior towards 1-octanol and that ncx-6 is required for the expulsion of waste during the last step of the DMP cycle in C. elegans. Data also show that ncx-6 and ncx-7 are not involved in the development of the ADL sensory neurons and intestine, and they also appear to have no effect on the calcium oscillations in the intestine.
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