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The present study was designed to demonstrate the function of calcium\u2010sensing receptor (CASR), which could recognize extracellular calcium as first messenger, during porcine egg activation. CASR expression was markedly upregulated following egg activation. Functionally, the addition of CASR agonist NPS R\u2010568 significantly enhanced pronuclear formation rate, while supplementation of CASR antagonist NPS2390 compromised egg activation. There was no change in NPS R\u2010568 group compared with control group when the egg activation was performed without extracellular calcium addition. The addition of NPS2390 precluded the activation\u2010dependent [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> rise. When egg activation was conducted in intracellular Ca<jats:sup>2+<\/jats:sup> chelator BAPTA\u2010AM and NPS R\u2010568 containing medium, CASR function was abolished. Meanwhile, CASR activation increased the level of the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> effector p\u2010CAMKII, and the presence of KN\u201093, an inhibitor of CAMKII, significantly reduced the CASR\u2010mediated increasement of pronuclear formation rate. Furthermore, the increase of CASR expression following activation was reversed by inhibiting CAMKII activity, supporting a positive feedback loop between CAMKII and CASR. Altogether, these findings provide a new pathway of egg activation about CASR, as the extracellular Ca<jats:sup>2+<\/jats:sup> effector, promotes egg activation via its downstream effector and upstream regulator CAMKII.<\/jats:p>","DOI":"10.1002\/mrd.23322","type":"journal-article","created":{"date-parts":[[2020,2,4]],"date-time":"2020-02-04T02:23:15Z","timestamp":1580782995000},"page":"598-606","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The extracellular calcium\u2010sensing receptor promotes porcine egg activation via calcium\/calmodulin\u2010dependent protein kinase II"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9657-7717","authenticated-orcid":false,"given":"Cong","family":"Liu","sequence":"first","affiliation":[{"name":"School of Basic Medical Science Wuhan University  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huage","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Agrobiotechnology, College of Biological Sciences China Agricultural University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Agrobiotechnology, College of Biological Sciences China Agricultural University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tengfei","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Agrobiotechnology, College of Biological Sciences China Agricultural University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangwei","family":"Fu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology China Agricultural University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng","family":"Cui","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Agrobiotechnology, College of Biological Sciences China Agricultural University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shien","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology China Agricultural University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1951-5448","authenticated-orcid":false,"given":"Yunpeng","family":"Hou","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Agrobiotechnology, College of Biological Sciences China Agricultural University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,2,3]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_7_2_1","DOI":"10.1016\/j.jsbmb.2015.02.006"},{"doi-asserted-by":"publisher","key":"e_1_2_7_3_1","DOI":"10.1016\/j.bbamcr.2015.02.011"},{"doi-asserted-by":"publisher","key":"e_1_2_7_4_1","DOI":"10.1038\/366575a0"},{"doi-asserted-by":"publisher","key":"e_1_2_7_5_1","DOI":"10.1152\/physrev.2001.81.1.239"},{"doi-asserted-by":"publisher","key":"e_1_2_7_6_1","DOI":"10.1074\/jbc.M708087200"},{"doi-asserted-by":"publisher","key":"e_1_2_7_7_1","DOI":"10.1006\/scdb.2000.0215"},{"issue":"2","key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1158\/0008-5472.493.65.2","article-title":"Calcium sensing receptor in human colon carcinoma: Interaction with Ca(2+) and 1,25\u2010dihydroxyvitamin D(3)","volume":"65","author":"Chakrabarty S.","year":"2005","journal-title":"Cancer Research"},{"issue":"11","key":"e_1_2_7_9_1","first-page":"1124","article-title":"Effects of calcium\u2010sensitive receptors on 11beta\u2010hydroxysteroid dehydrogenase type 2 and cortisol in neonatal mice with persistent pulmonary hypertension","volume":"21","author":"Chen Z. 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