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Physiol. Genomics 37: 175-186, 2009. First published March 24, 2009; doi:10.1152/physiolgenomics.00017.2009
1094-8341/09 $8.00
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Received 22 January 2009; accepted in final form 24 March 2009.
Physiological Genomics 37:175-186 (2009)
1094-8341/09 $8.00 © 2009 American Physiological Society

Call For Papers: Comparative Genomics

Molecular evolution of the junctophilin gene family

Alejandro Garbino 1,2, Ralph J. van Oort 1, Sayali S. Dixit 1, Andrew P. Landstrom 3, Michael J. Ackerman 3 and Xander H. T. Wehrens 1,2,4

1 Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas
2 Translational Biology and Molecular Medicine Program, Baylor College of Medicine, Houston, Texas
3 Departments of Molecular Pharmacology & Experimental Therapeutics, Medicine, and Pediatrics/Divisions of Cardiovascular Diseases and Pediatric Cardiology, Mayo Clinic, Rochester, Minnesota
4 Medicine (in Cardiology), Baylor College of Medicine, Houston, Texas

Junctophilins (JPHs) are members of a junctional membrane complex protein family important for the physical approximation of plasmalemmal and sarcoplasmic/endoplasmic reticulum membranes. As such, JPHs facilitate signal transduction in excitable cells between plasmalemmal voltage-gated calcium channels and intracellular calcium release channels. To determine the molecular evolution of the JPH gene family, we performed a phylogenetic analysis of over 60 JPH genes from over 40 species and compared conservation across species and different isoforms. We found that JPHs are evolutionary highly conserved, in particular the membrane occupation and recognition nexus motifs found in all species. Our data suggest that an ancestral form of JPH arose at the latest in a common metazoan ancestor and that in vertebrates four isoforms arose, probably following two rounds of whole genome duplications. By combining multiple prediction techniques with sequence alignments, we also postulate the presence of new important functional regions and candidate sites for posttranslational modifications. The increasing number of available sequences yields significant insight into the molecular evolution of JPHs. Our analysis is consistent with the emerging concept that JPHs serve dual important functions in excitable cells: structural assembly of junctional membrane complexes and regulation of intracellular calcium signaling pathways.

calcium signaling; junctional membrane complex; excitation-contraction coupling; MORN motif; excitable cells







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