Proper phosphorylation of septin 12 regulates septin 4 and soluble adenylyl cyclase expression to induce sperm capacitation

doi:10.1002/jcp.30951

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Title:	Proper phosphorylation of septin 12 regulates septin 4 and soluble adenylyl cyclase expression to induce sperm capacitation
Authors:	Wang, Han-Yu Shen, Yi-Ru Tsai, Yung-Chieh Wu, Shang-Rung Wang, Chia-Yih Kuo, Pao-Lin
Contributors:	Natl Cheng Kung Univ, Inst Basic Med Sci, Coll Med Natl Cheng Kung Univ, Coll Med, Dept Obstet & Gynecol Chia Nan Univ Pharm & Sci, Chi Mei Med Ctr, Dept Obstet & Gynecol Sport Management & Biotechno Natl Cheng Kung Univ, Inst Oral Med, Coll Med Natl Cheng Kung Univ, Coll Med, Dept Cell Biol & Anat Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Obstet & Gynecol
Keywords:	male fertility SEPTIN sperm capacitation
Date:	2023
Issue Date:	2024-12-25 11:05:20 (UTC+8)
Publisher:	WILEY
Abstract:	Septin-based ring complexes maintain the sperm annulus. Defective annular structures are observed in the sperm of Sept12- and Sept4-null mice. In addition, sperm capacitation, a process required for proper fertilization, is inhibited in Sept4-null mice, implying that the sperm annulus might play a role in controlling sperm capacitation. Hence, we analyzed sperm capacitation of sperm obtained from SEPT12 Ser196 phosphomimetic (S196E), phosphorylation-deficient (S196A), and SEPT4-depleted mutant mice. Capacitation was reduced in the sperm of both the Sept12 S196E- and Sept12 S196A-knock-in mice. The protein levels of septins, namely, SEPT4 and SEPT12, were upregulated, and these proteins were concentrated in the sperm annulus during capacitation. Importantly, the expression of soluble adenylyl cyclase (sAC), a key enzyme that initiates capacitation, was upregulated, and sAC was recruited to the sperm annulus following capacitation stimulation. We further found that SEPT12, SEPT4, and sAC formed a complex and colocalized to the sperm annulus. Additionally, sAC expression was reduced and disappeared in the annulus of the SEPT12 S196E- and S196A-mutant mouse sperm. In the sperm of the SEPT4-knockout mice, sAC did not localize to the annulus. Thus, our data demonstrate that SEPT12 phosphorylation status and SEPT4 activity jointly regulate sAC protein levels and annular localization to induce sperm capacitation.
Relation:	Journal of Cellular Physiology, v.238, n.3, pp.597-609
Appears in Collections:	[Offices] 456

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