Unconventional endocannabinoid signaling governs sperm activation via the sex hormone progesterone

被引：184

作者：

Miller, Melissa R. ^{[1
]}

Mannowetz, Nadja ^{[1
]}

Iavarone, Anthony T. ^{[2
]}

Safavi, Rojin ^{[1
]}

Gracheva, Elena O. ^{[3
,4
]}

Smith, James F. ^{[5
]}

Hill, Rose Z. ^{[1
]}

Bautista, Diana M. ^{[1
]}

Kirichok, Yuriy ^{[6
]}

Lishko, Polina V. ^{[1
]}

机构：

[1] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA

[2] Univ Calif Berkeley, Chem Mass Spectrometry Facil QB3, 229 Stanley Hall, Berkeley, CA 94720 USA

[3] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, 333 Cedar St, New Haven, CT 06536 USA

[4] Yale Univ, Sch Med, Dept Neurosci, Program Cellular Neurosci Neurodegenerat & Repair, 333 Cedar St, New Haven, CT 06536 USA

[5] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA

[6] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA

来源：

SCIENCE | 2016年 / 352卷 / 6285期

关键词：

MALE-FERTILITY; CA2+ CHANNEL; NONGENOMIC ACTIONS; STEROID-HORMONES; PATCH-CLAMP; SPERMATOZOA; MOTILITY; 2-ARACHIDONOYLGLYCEROL; PRINCIPAL; RECEPTOR;

D O I：

10.1126/science.aad6887

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Steroids regulate cell proliferation, tissue development, and cell signaling via two pathways: a nuclear receptor mechanism and genome-independent signaling. Sperm activation, egg maturation, and steroid-induced anesthesia are executed via the latter pathway, the key components of which remain unknown. Here, we present characterization of the human sperm progesterone receptor that is conveyed by the orphan enzyme alpha/beta hydrolase domain-containing protein 2 (ABHD2). We show that ABHD2 is highly expressed in spermatozoa, binds progesterone, and acts as a progesterone-dependent lipid hydrolase by depleting the endocannabinoid 2-arachidonoylglycerol (2AG) from plasma membrane. The 2AG inhibits the sperm calcium channel (CatSper), and its removal leads to calcium influx via CatSper and ensures sperm activation. This study reveals that progesterone-activated endocannabinoid depletion by ABHD2 is a general mechanism by which progesterone exerts its genome-independent action and primes sperm for fertilization.

引用

页码：555 / 559

页数：5

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