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PLoS One. 2014 Jul 3;9(7):e100694. doi: 10.1371/journal.pone.0100694. eCollection 2014.

Ancient origins of RGK protein function: modulation of voltage-gated calcium channels preceded the protostome and deuterostome split.

Author information

1
Laboratory of Molecular Physiology, Section on Transmitter Signaling, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, United States of America.
2
Department of Biochemistry & Molecular Biology, Faculty of Life Sciences, Institute for Structural Biology, Tel Aviv University, Ramat Aviv, Israel.
3
Laboratory of Molecular Physiology, Section on Model Synaptic Systems, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, United States of America.

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.

PMID:
24992013
PMCID:
PMC4081519
DOI:
10.1371/journal.pone.0100694
[Indexed for MEDLINE]
Free PMC Article

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