PUBLICATION

Ancient Origins of RGK Protein Function: Modulation of Voltage-Gated Calcium Channels Preceded the Protostome and Deuterostome Split

Authors
Puhl, H.L., Lu, V.B., Won, Y.J., Sasson, Y., Hirsch, J.A., Ono, F., Ikeda, S.R.
ID
ZDB-PUB-140706-12
Date
2014
Source
PLoS One   9: e100694 (Journal)
Registered Authors
Ono, Fumihito
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Calcium Channels, L-Type/genetics*
  • Calcium Channels, L-Type/metabolism
  • Drosophila Proteins/genetics*
  • Drosophila Proteins/metabolism
  • Drosophila melanogaster
  • Evolution, Molecular*
  • Molecular Sequence Data
  • Monomeric GTP-Binding Proteins/genetics*
  • Monomeric GTP-Binding Proteins/metabolism
  • Rats
  • Rats, Wistar
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • ras Proteins/genetics*
  • ras Proteins/metabolism
PubMed
24992013 Full text @ PLoS One
Abstract
RGK proteins, Gem, Rad, Rem1, and Rem2, are members of the Ras superfamily of small GTP-binding proteins that interact with Ca2+ channel β subunits to modify voltage-gated Ca2+ channel function. In addition, RGK proteins affect several cellular processes such as cytoskeletal rearrangement, neuronal dendritic complexity, and synapse formation. To probe the phylogenetic origins of RGK protein-Ca2+ channel interactions, we identified potential RGK-like protein homologs in genomes for genetically diverse organisms from both the deuterostome and protostome animal superphyla. RGK-like protein homologs cloned from Danio rerio (zebrafish) and Drosophila melanogaster (fruit flies) expressed in mammalian sympathetic neurons decreased Ca2+ current density as reported for expression of mammalian RGK proteins. Sequence alignments from evolutionarily diverse organisms spanning the protostome/deuterostome divide revealed conservation of residues within the RGK G-domain involved in RGK protein - Cavβ subunit interaction. In addition, the C-terminal eleven residues were highly conserved and constituted a signature sequence unique to RGK proteins but of unknown function. Taken together, these data suggest that RGK proteins, and the ability to modify Ca2+ channel function, arose from an ancestor predating the protostomes split from deuterostomes approximately 550 million years ago.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping