Male infertility in mice lacking the store-operated Ca(2+) channel Orai1
| Autor: | Eugenia H. Goulding, James W. Putney, Edward M. Eddy, Gary S. Bird, Kyathanahalli S. Janardhan, Felicity M. Davis, Connie A. Cummings, Diane M. D’Agostin |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Cell type ORAI1 Protein Physiology Somatic cell Cell Separation Biology Endoplasmic Reticulum Article Male infertility 03 medical and health sciences Mice 0302 clinical medicine Internal medicine medicine Animals Calcium Signaling Molecular Biology Infertility Male Reproductive function Spermatid ORAI1 Endoplasmic reticulum Cell Biology medicine.disease 030104 developmental biology Endocrinology medicine.anatomical_structure 030220 oncology & carcinogenesis Calcium Female Signal transduction |
| Zdroj: | Cell calcium. 59(4) |
| ISSN: | 1532-1991 |
| Popis: | Store-operated calcium entry (SOCE) is an important Ca(2+) influx pathway in somatic cells. In addition to maintaining endoplasmic reticulum (ER) Ca(2+) stores, Ca(2+) entry through store-operated channels regulates essential signaling pathways in numerous cell types. Patients with mutations in the store-operated channel subunit ORAI1 exhibit defects in store-operated Ca(2+) influx, along with severe immunodeficiency, congenital myopathy and ectodermal dysplasia. However, little is known about the functional role of ORAI1 in germ cells and reproductive function in mice, or in men, since men with loss-of-function or null mutations in ORAI1 rarely survive to reproductive age. In this study, we investigated the role of ORAI1 in male reproductive function. We reveal that Orai1(-/-) male mice are sterile and have severe defects in spermatogenesis, with prominent deficiencies in mid- to late-stage elongating spermatid development. These studies establish an essential in vivo role for store-operated ORAI1 channels in male reproductive function and identify these channels as potential non-steroidal regulators of male fertility. |
| Databáze: | OpenAIRE |
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