title: Evidence for functional diversity between the voltage-gated proton channel Hv1 and its closest related protein HVRP1.
abstract: The Hv1 channel and voltage-sensitive phosphatases share with voltage-gated sodium, potassium, and calcium channels the ability to detect changes in membrane potential through voltage-sensing domains (VSDs). However, they lack the pore domain typical of these other channels. NaV, KV, and CaV proteins can be found in neurons and muscles, where they play important roles in electrical excitability. In contrast, VSD-containing proteins lacking a pore domain are found in non-excitable cells and are not involved in neuronal signaling. Here, we report the identification of HVRP1, a protein related to the Hv1 channel (from which the name Hv1 Related Protein 1 is derived), which we find to be expressed primarily in the central nervous system, and particularly in the cerebellum. Within the cerebellar tissue, HVRP1 is specifically expressed in granule neurons, as determined by in situ hybridization and immunohistochemistry. Analysis of subcellular distribution via electron microscopy and immunogold labeling reveals that the protein localizes on the post-synaptic side of contacts between glutamatergic mossy fibers and the granule cells. We also find that, despite the similarities in amino acid sequence and structural organization between Hv1 and HVRP1, the two proteins have distinct functional properties. The high conservation of HVRP1 in vertebrates and its cellular and subcellular localizations suggest an important function in the nervous system.
authors.affiliation: Department of Physiology and Biophysics, University of California Irvine, Irvine, California, United States of America.
authors.forename: Iris H
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Department of Physiology and Biophysics, University of California Irvine, Irvine, California, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Hevezi
authors.affiliation: Department of Anatomy and Neurobiology, University of California Irvine, Irvine, California, United States of America.
authors.forename: Csaba
authors.initials: C
authors.lastname: Varga
authors.affiliation: Department of Physiology and Biophysics, University of California Irvine, Irvine, California, United States of America.
authors.forename: Medha M
authors.initials: MM
authors.lastname: Pathak
authors.affiliation: Department of Physiology and Biophysics, University of California Irvine, Irvine, California, United States of America.
authors.forename: Liang
authors.initials: L
authors.lastname: Hong
authors.affiliation: Department of Physiology and Biophysics, University of California Irvine, Irvine, California, United States of America.
authors.forename: Dennis
authors.initials: D
authors.lastname: Ta
authors.affiliation: Department of Physiology and Biophysics, University of California Irvine, Irvine, California, United States of America.
authors.forename: Chau T
authors.initials: CT
authors.lastname: Tran
authors.affiliation: Department of Physiology and Biophysics, University of California Irvine, Irvine, California, United States of America.
authors.forename: Albert
authors.initials: A
authors.lastname: Zlotnik
authors.affiliation: Department of Anatomy and Neurobiology, University of California Irvine, Irvine, California, United States of America.
authors.forename: Ivan
authors.initials: I
authors.lastname: Soltesz
authors.affiliation: Department of Physiology and Biophysics, University of California Irvine, Irvine, California, United States of America.
authors.forename: Francesco
authors.initials: F
authors.lastname: Tombola
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002531:Cerebellum / Q000378:metabolism*; D017124:Conserved Sequence; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D010802:Phylogeny; D057907:Post-Synaptic Density / Q000378:metabolism*
chemical_list: C510235:HVCN1 protein, human; C540876:Hv1 proton channel, mouse; D007473:Ion Channels