Ancient association between cation leak channels and Midi proteins is conserved in fungi and animals

作者：Ghezzi Alfredo^*; Liebeskind Benjamin J; Thompson Ammon; Atkinson Nigel S; Zakon Harold H

来源：Frontiers in Molecular Neuroscience, 2014, 7.

DOI：10.3389/fnmol.2014.00015

• Drosophila
• Cch1
• RNAi
• Social Space Index
• Circadian Rhythms
• phenocopy

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 Midi, the subunit of the yeast calcium channel. These proteins all share a cysteine-rich region that is necessary for Midi function in yeast. We validate this predicted association by showing that the Midi 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 Midi 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.

• 出版日期2014-3-7