Cyclic Nucleotide-Specific Optogenetics Highlights Compartmentalization of the Sperm Flagellum into cAMP Microdomains
Cyclic Nucleotide-Specific Optogenetics Highlights Compartmentalization of the Sperm Flagellum into cAMP Microdomains
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DOI：
10.3390/cells8070648
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发表时间：
2019-07-01
期刊：
影响因子：
6
通讯作者：
Wachten, Dagmar
中科院分区：
文献类型：
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作者：
Raju, Diana N.;Hansen, Jan N.;Wachten, Dagmar
在女性生殖道内，哺乳动物的精子经历了一个称为获能的成熟过程，这为精子穿越输卵管并使卵子受精做好了准备。精子获能和运动受3‘，5’-环磷酸腺苷(CAMP)控制。在这里，我们展示了光遗传学，即通过基因编码的光激活蛋白控制细胞信号，允许操纵精子鞭毛中的cAMP动态，从而通过光来控制精子的获能和运动。为此，我们使用了表达光激活的磷酸二酯酶Lapd或光激活的腺苷环化酶BPAC的精子。LAPD或BPAC结合药物干预对cAMP的控制提供了时空上的精确度，并使我们能够探索哺乳动物精子中cAMP区域化的生理功能。
Inside the female genital tract, mammalian sperm undergo a maturation process called capacitation, which primes the sperm to navigate across the oviduct and fertilize the egg. Sperm capacitation and motility are controlled by 3',5'-cyclic adenosine monophosphate (cAMP). Here, we show that optogenetics, the control of cellular signaling by genetically encoded light-activated proteins, allows to manipulate cAMP dynamics in sperm flagella and, thereby, sperm capacitation and motility by light. To this end, we used sperm that express the light-activated phosphodiesterase LAPD or the photo-activated adenylate cyclase bPAC. The control of cAMP by LAPD or bPAC combined with pharmacological interventions provides spatiotemporal precision and allows to probe the physiological function of cAMP compartmentalization in mammalian sperm.