Cell-penetrating peptides, targeting the regulation of store-operated channels, slow decay of the progesterone-induced [Ca 2+ ] i signal in human sperm
Abstract
Previous work has provided evidence for involvement of store-operated channels (SOCs) in [Ca(2+)]i signalling of human sperm, including a contribution to the transient [Ca(2+)]i elevation that occurs upon activation of CatSper, a sperm-specific cation channel localized to the flagellum, by progesterone. To further investigate the potential involvement of SOCs in the generation of [Ca(2+)]i signals in human sperm, we have used cell-penetrating peptides containing the important basic sequence KIKKK, part of the STIM-Orai activating region/CRAC activating domain (SOAR/CAD) of the regulatory protein stromal interaction molecule 1. SOAR/CAD plays a key role in controlling the opening of SOCs, which occurs upon mobilization of stored Ca(2+). Resting [Ca(2+)]i temporarily decreased upon application of KIKKK peptide (3-4 min), but scrambled KIKKK peptide had a similar effect, indicating that this action was not sequence-specific. However, in cells pretreated with KIKKK, the transient [Ca(2+)]i elevation induced by stimulation with progesterone decayed significantly more slowly than in parallel controls and in cells pretreated with scrambled KIKKK peptide. Examination of single-cell responses showed that this effect was due, at least in part, to an increase in the proportion of cells in which the initial transient was maintained for an extended period, lasting up to 10 min in a subpopulation of cells. We hypothesize that SOCs contribute to the progesterone-induced [Ca(2+)]i transient, and that interference with the regulatory mechanisms of SOC delays their closure, causing a prolongation of the [Ca(2+)]i transient.Citation
Cell-penetrating peptides, targeting the regulation of store-operated channels, slow decay of the progesterone-induced [Ca 2+ ] i signal in human sperm 2015, 21 (7):563 Molecular Human ReproductionPublisher
Oxford University Press on behalf of the European Society of Human Reproduction and EmbryologyJournal
Molecular Human ReproductionAdditional Links
https://academic.oup.com/molehr/article/21/7/563/2459741Type
Journal articleLanguage
enDescription
© 2015 The Authors. Published by Oxford University Press. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1093/molehr/gav019ISSN
1360-99471460-2407
Sponsors
L.L. was supported by theWellcome Trust (Grant #086470). J.M. was supported by a University of Birmingham Teaching Assistantship. Funding to pay the Open Access publication charges for this article was provided by . . .ae974a485f413a2113503eed53cd6c53
10.1093/molehr/gav019
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