title: The in vivo TRPV6 protein starts at a non-AUG triplet, decoded as methionine, upstream of canonical initiation at AUG.
abstract: TRPV6 channels function as epithelial Ca(2+) entry pathways in the epididymis, prostate, and placenta. However, the identity of the endogenous TRPV6 protein relies on predicted gene coding regions and is only known to a certain level of approximation. We show that in vivo the TRPV6 protein has an extended N terminus. Translation initiates at a non-AUG codon, at ACG, which is decoded by methionine and which is upstream of the annotated AUG, which is not used for initiation. The in vitro properties of channels formed by the extended full-length TRPV6 proteins and the so-far annotated and smaller TRPV6 are similar, but the extended N terminus increases trafficking to the plasma membrane and represents an additional scaffold for channel assembly. The increased translation of the smaller TRPV6 cDNA version may overestimate the in vivo situation where translation efficiency may represent an additional mechanism to tightly control the TRPV6-mediated Ca(2+) entry to prevent deleterious Ca(2+) overload.
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, 66421 Homburg, Germany. Electronic address: claudia.fecher-trost@uks.eu.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fecher-Trost
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, 66421 Homburg, Germany. Electronic address: ulrich.wissenbach@uks.eu.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wissenbach
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, 66421 Homburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Beck
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, 66421 Homburg, Germany.
authors.forename: Pascal
authors.initials: P
authors.lastname: Schalkowsky
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, 66421 Homburg, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Stoerger
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, 66421 Homburg, Germany.
authors.forename: Janka
authors.initials: J
authors.lastname: Doerr
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, 66421 Homburg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Dembek
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, 66421 Homburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Simon-Thomas
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, 66421 Homburg, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Weber
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, 66421 Homburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Wollenberg
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruppert
authors.affiliation: Institut für Anatomie und Zellbiologie, Justus Liebig Universität Gieβen, Aulweg 123, 35385 Giessen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Middendorff
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, 66421 Homburg, Germany.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Maurer
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, 66421 Homburg, Germany. Electronic address: veit.flockerzi@uks.eu.
authors.forename: Veit
authors.initials: V
authors.lastname: Flockerzi
mesh_terms: D015220:Calcium Channels / Q000096:biosynthesis* / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D018387:Codon, Initiator / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008715:Methionine; D014176:Protein Biosynthesis / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D050916:TRPV Cation Channels / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D015220:Calcium Channels; D018387:Codon, Initiator; D050916:TRPV Cation Channels; C422827:TRPV6 protein, human; D008715:Methionine
keywords: Antibodies; Calcium Channels; Mass Spectrometry (MS); TRP Channels; TRPV6; Translation; Translation Initiation at Non-AUG