title: SLO BK Potassium Channels Couple Gap Junctions to Inhibition of Calcium Signaling in Olfactory Neuron Diversification.
abstract: The C. elegans AWC olfactory neuron pair communicates to specify asymmetric subtypes AWCOFF and AWCON in a stochastic manner. Intercellular communication between AWC and other neurons in a transient NSY-5 gap junction network antagonizes voltage-activated calcium channels, UNC-2 (CaV2) and EGL-19 (CaV1), in the AWCON cell, but how calcium signaling is downregulated by NSY-5 is only partly understood. Here, we show that voltage- and calcium-activated SLO BK potassium channels mediate gap junction signaling to inhibit calcium pathways for asymmetric AWC differentiation. Activation of vertebrate SLO-1 channels causes transient membrane hyperpolarization, which makes it an important negative feedback system for calcium entry through voltage-activated calcium channels. Consistent with the physiological roles of SLO-1, our genetic results suggest that slo-1 BK channels act downstream of NSY-5 gap junctions to inhibit calcium channel-mediated signaling in the specification of AWCON. We also show for the first time that slo-2 BK channels are important for AWC asymmetry and act redundantly with slo-1 to inhibit calcium signaling. In addition, nsy-5-dependent asymmetric expression of slo-1 and slo-2 in the AWCON neuron is necessary and sufficient for AWC asymmetry. SLO-1 and SLO-2 localize close to UNC-2 and EGL-19 in AWC, suggesting a role of possible functional coupling between SLO BK channels and voltage-activated calcium channels in AWC asymmetry. Furthermore, slo-1 and slo-2 regulate the localization of synaptic markers, UNC-2 and RAB-3, in AWC neurons to control AWC asymmetry. We also identify the requirement of bkip-1, which encodes a previously identified auxiliary subunit of SLO-1, for slo-1 and slo-2 function in AWC asymmetry. Together, these results provide an unprecedented molecular link between gap junctions and calcium pathways for terminal differentiation of olfactory neurons.
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.|Molecular and Developmental Biology Graduate Program, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Amel
authors.initials: A
authors.lastname: Alqadah
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Hsieh
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio, United States of America.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Schumacher
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio, United States of America.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biology and Howard Hughes Medical Institute, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Sean A
authors.initials: SA
authors.lastname: Merrill
authors.affiliation: Molecular and Developmental Biology Graduate Program, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Grethel
authors.initials: G
authors.lastname: Millington
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio, United States of America.
authors.forename: Brittany
authors.initials: B
authors.lastname: Bayne
authors.affiliation: Department of Biology and Howard Hughes Medical Institute, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Erik M
authors.initials: EM
authors.lastname: Jorgensen
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Chiou-Fen
authors.initials: CF
authors.lastname: Chuang
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics*; D015220:Calcium Channels / Q000096:biosynthesis / Q000235:genetics*; D020013:Calcium Signaling / Q000235:genetics; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D017629:Gap Junctions / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics*; D018034:Olfactory Receptor Neurons / Q000378:metabolism; D012903:Smell / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D015220:Calcium Channels; C109164:Egl-19 protein, C elegans; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009124:Muscle Proteins; C402625:SLO-2 protein, C elegans; C494845:slo-1 protein, C elegans; C093204:unc-2 protein, C elegans