title: Ancient association between cation leak channels and Mid1 proteins is conserved in fungi and animals.
abstract: Neuronal resting potential can tune the excitability of neural networks, affecting downstream behavior. Sodium leak channels (NALCN) play a key role in rhythmic behaviors by helping set, or subtly changing neuronal resting potential. The full complexity of these newly described channels is just beginning to be appreciated, however. NALCN channels can associate with numerous subunits in different tissues and can be activated by several different peptides and second messengers. We recently showed that NALCN channels are closely related to fungal calcium channels, which they functionally resemble. Here, we use this relationship to predict a family of NALCN-associated proteins in animals on the basis of homology with the yeast protein Mid1, the subunit of the yeast calcium channel. These proteins all share a cysteine-rich region that is necessary for Mid1 function in yeast. We validate this predicted association by showing that the Mid1 homolog in Drosophila, encoded by the CG33988 gene, is coordinately expressed with NALCN, and that knockdown of either protein creates identical phenotypes in several behaviors associated with NALCN function. The relationship between Mid1 and leak channels has therefore persisted over a billion years of evolution, despite drastic changes to both proteins and the organisms in which they exist.
authors.affiliation: Department of Neuroscience, University of Texas at Austin Austin, TX, USA.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ghezzi
authors.affiliation: Department of Integrative Biology, University of Texas at Austin TX, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Liebeskind
authors.affiliation: Department of Integrative Biology, University of Texas at Austin TX, USA.
authors.forename: Ammon
authors.initials: A
authors.lastname: Thompson
authors.affiliation: Department of Neuroscience, University of Texas at Austin Austin, TX, USA.
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Atkinson
authors.affiliation: Department of Neuroscience, University of Texas at Austin Austin, TX, USA ; Department of Integrative Biology, University of Texas at Austin TX, USA ; Marine Biological Laboratory, The Josephine Bay Paul Center Woods Hole, MA, USA.
authors.forename: Harold H
authors.initials: HH
authors.lastname: Zakon
keywords: Cch1; Circadian Rhythms; Drosophila; RNAi; Social Space Index; phenocopy