Sperm channel diversity and functional multiplicity

Darszon, Alberto; Acevedo-Fernández, Juan José; Galindo, Blanca E.; Hernández‐González, Enrique O.; Nishigaki, Takuya; Treviño, Claudia L.; Wood, Christopher D.; Beltrán, Carmen

doi:10.1530/rep.1.00612

Cited by 172 publications

(183 citation statements)

References 103 publications

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“…1E and SI Appendix, Fig. S2B) (23)(24)(25)(26). Best1 transcripts were first evident at mouse postnatal day (PN) 19, with a strong increase until PN30, where it reached steady-state adulthood levels.…”

Section: Expression Profiling Suggests a Role For Best1 In Mouse Spermentioning

confidence: 99%

Bestrophin 1 is indispensable for volume regulation in human retinal pigment epithelium cells

Milenkovic¹,

Brandl

Milenkovic³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

113

142

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In response to cell swelling, volume-regulated anion channels (VRACs) participate in a process known as regulatory volume decrease (RVD). Only recently, first insight into the molecular identity of mammalian VRACs was obtained by the discovery of the leucine-rich repeats containing 8A (LRRC8A) gene. Here, we show that bestrophin 1 (BEST1) but not LRRC8A is crucial for volume regulation in human retinal pigment epithelium (RPE) cells. Whole-cell patch-clamp recordings in RPE derived from human-induced pluripotent stem cells (hiPSC) exhibit an outwardly rectifying chloride current with characteristic functional properties of VRACs. This current is severely reduced in hiPSC-RPE cells derived from macular dystrophy patients with pathologic BEST1 mutations. Disruption of the orthologous mouse gene (Best1 −/− ) does not result in obvious retinal pathology but leads to a severe subfertility phenotype in agreement with minor endogenous expression of Best1 in murine RPE but highly abundant expression in mouse testis. Sperm from Best1 −/− mice showed reduced motility and abnormal sperm morphology, indicating an inability in RVD. Together, our data suggest that the molecular identity of VRACs is more complex-that is, instead of a single ubiquitous channel, VRACs could be formed by cell type-or tissue-specific subunit composition. Our findings provide the basis to further examine VRAC diversity in normal and diseased cell physiology, which is key to exploring novel therapeutic approaches in VRAC-associated pathologies.bestrophin 1 | volume-regulated anion channel | induced pluripotent stem cell | retinal pigment epithelium | mouse sperm

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Section: Expression Profiling Suggests a Role For Best1 In Mouse Spermentioning

confidence: 99%

Bestrophin 1 is indispensable for volume regulation in human retinal pigment epithelium cells

Milenkovic¹,

Brandl

Milenkovic³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

113

142

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“…Chemotaxis, however, is not the sole response of swimming sperm that depends on Ca 2+ -regulation of flagellar movement. Many kinds of ion channels and other membrane proteins related to Ca 2+ transport in sperm membrane (Darszon et al, 2006) may well be involved, through their organized functioning, in the Ca 2+ -dependent regulation of flagellar movement in swimming behaviours of sperm.…”

Section: Camentioning

confidence: 99%

Mechanism Regulating Ca2+-dependent Mechanosensory Behaviour in Sea Urchin Spermatozoa

Kambara

Shiba

Yoshida

et al. 2011

Cell Struct. Funct.

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ABSTRACT. Flagellar movement of the sea urchin sperm is regulated by intracellular Ca 2+ . Flagellasialin, a polysialic acid-containing glycoprotein, as well as other membrane proteins seems responsible for the Ca 2+ control. To elucidate the mechanism of Ca 2+ dynamics underlying flagellar movement, we analysed the sperm's mechanosensory behavioural responses by using microtechniques. In sea water containing 10 mM Ca 2+ , the sperm swim in circular paths. When a mechanical stimulus was applied to the sperm head with a glass microstylus, the sperm showed a series of flagellar responses, consisting of a stoppage of beating (quiescence) and a recovery of swimming in a straight path, followed by swimming in a circular path again; as the result the sperm avoided the obstacle. Ca 2+ -imaging with Fluo-4 showed that the intracellular Ca 2+ was high in the quiescence and gradually decreased after that. The effects of blockers and antibodies against candidate components revealed that the Ca 2+ influx was induced by Ca 2+ channels and the Ca 2+ efflux was induced by a flagellasialin-related Ca 2+ -efflux system, plasma membrane Ca 2+ -ATPases and the K + -dependent Na + /Ca 2+ exchanger. The results show that the Ca 2+ -dependent mechanosensory behaviour of the sea urchin sperm is regulated by organized functioning of the membrane environment including the plasma membrane proteins and flagellasialin.

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“…It is known that a sustained calcium increase through store-operated calcium channels drives exocytosis (19,20). During exocytosis, there are some parallel and concomitant steps necessary to achieve AR that occurs thereafter.…”

mentioning

confidence: 99%

ADP Ribosylation Factor 6 (ARF6) Promotes Acrosomal Exocytosis by Modulating Lipid Turnover and Rab3A Activation

Pelletán

Suhaiman

Vaquer

et al. 2015

Journal of Biological Chemistry

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Background: Sperm acrosomal exocytosis requires GTPases, SNAREs, and a complex lipid signaling. Results: Exocytic stimuli promote ARF6 activation, which accomplishes exocytosis by stimulating PLC and Rab3A. Conclusion: ARF6 induces acrosome calcium efflux and assembles the fusion machinery leading to membrane fusion. Significance: This study explores a novel molecular link between ARF6, PLC, and Rab3A and provides insight into the molecular mechanisms of exocytosis and reproduction.

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Sperm channel diversity and functional multiplicity

Cited by 172 publications

References 103 publications

Bestrophin 1 is indispensable for volume regulation in human retinal pigment epithelium cells

Bestrophin 1 is indispensable for volume regulation in human retinal pigment epithelium cells

Mechanism Regulating Ca2+-dependent Mechanosensory Behaviour in Sea Urchin Spermatozoa

ADP Ribosylation Factor 6 (ARF6) Promotes Acrosomal Exocytosis by Modulating Lipid Turnover and Rab3A Activation

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