Excision of Trpv6 Gene Leads to Severe Defects in Epididymal Ca2+ Absorption and Male Fertility Much Like Single D541A Pore Mutation

Abstract

Background: The TRPV6D541A pore mutation abrogates epididymal Ca 2ϩ absorption causing hypofertility in mice, raising the possibility of residual TRPV6 D541A channel activity. Results: Trpv6 deletion reduces fertility parameters to the same extent as the D541A pore mutation. Conclusion:The D541A pore mutation leads to complete inactivation of TRPV6 channels in epididymal epithelium. Significance: Targeted mutations in mice help to understand the function of TRPV6 proteins in native systems.

Thermosensitive ion channel TRPV1 is endogenously expressed in the sperm of a fresh water teleost fish (Labeo rohita) and regulates sperm motility

“…33,34 In the same context, involvement of TRPV6 in male fertility and sterility has been demonstrated. 35,36 Involvement of TRP channels in reproduction may have more important roles and is not limited just to sperm cell survival and movement required for fertilization. TRP channels may even have roles in the spermatogenesis as well, an important aspect which might be evolutionary conserved as well.…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…TRPV6 controls the extracellular Ca 2+ concentration toward the distal segments of the epididymal duct, which is essential for survival of spermatozoa. Loss of functional channels causes severely impaired fertility due to a reduction in motility and fertilization capacity of sperms (Weissgerber et al, 2012). In the skin, TRPV6 is a key element in Ca 2+ /1,25-dihydroxyvitamin D3-induced keratinocyte development (Lehen'kyi et al, 2007).…”

The in Vivo TRPV6 Protein Starts at a Non-AUG Triplet, Decoded as Methionine, Upstream of Canonical Initiation at AUG

“…After overexpression of its complementary DNA (cDNA) in the human embryonic kidney (HEK293) cell line, TRPV6 forms plasmalemmal ion channels leading to selective Ca 2ϩ influx as long as the intracellular Ca 2ϩ concentration is kept low by BAPTA or related chelators. Only recently, TRPV6 has been shown to be critical for Ca 2ϩ absorption through the epididymal and prostate epithelium (5,6). Both the replacement of a single amino acid residue within the TRPV6 channel pore, D542A, in mice or deletion of the wild-type TRPV6 gene in mice by gene targeting cause severe defects in male fertility, motility, and viability of sperm and a significant increase in the epididymal and prostatic luminal Ca 2ϩ concentrations.…”

“…For glutathione S-transferase (GST) pulldown assay a fragment of the TRPV6 cDNA (nucleotides Ϫ120 to ϩ78) was fused to the GST cDNA and cloned in pGEX2T (GE Healthcare). All cloning steps that required PCR amplification were done with the Phusion polymerase (5), and all cDNA constructs were sequenced before use.…”