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Mechanical Stimulation Activates Drosophila Eggs Via Trpm Channels COMMENTARY Anne E

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Mechanical Stimulation Activates Drosophila Eggs Via Trpm Channels COMMENTARY Anne E COMMENTARY Mechanical stimulation activates Drosophila eggs via Trpm channels COMMENTARY Anne E. Carlsona,1 At fertilization, the terminally differentiated egg be- they are actively forced out of the ovary (4). This finding gins a new life as a totipotent zygote. Egg activation gave rise to the hypothesis that mechanical pressure is an important process in this transformation to activates Drosophila eggs. Two observations supported totipotency, as activation represents the time when this mechanical activation hypothesis. First, Drosophila immature oocytes develop from a state of cellular qui- eggs can be activated in vitro by hypotonic solution; escence into one ready for embryogenesis. In PNAS, hypotonic solution made these oocytes swell to thereby Hu and Wolfner demonstrate that the Trpm ion chan- stretch the plasma membrane (4). Second, activation of + nel conducts a Ca2 influx into eggs from the fruit fly, Drosophila eggs was induced by their compression Drosophila melanogaster, to signal their activation (1). between a glass slide and coverslip, another condition Eggs from insects including fruit flies, bees, and that should stretch the plasma membrane (4). How do ants activate before fertilization when they are pushed eggs detect their compression as they are pushed out out of the ovary. Independence of egg activation from of the ovary? Often, mechanical forces derived from fertilization in insect eggs allowed for the evolution of stretch or compression of cells are detected by mechan- varied reproductive strategies ranging from parthenogenic ically gated ion channels. These plasma membrane- reproduction, where females produce daughters with no embedded proteins relay changes in the membrane male input, to sexual reproduction, where offspring tension into intracellular messages (5). Due to their are the result of maternal and paternal contributions ability to respond to mechanical activation, ion channels (2). Other species also separate activation and fertiliza- from the Trp family were proposed to mediate Drosophila tion. For example, eggs from zebrafish, an obligate egg activation. A role for a Trp channel in egg activation sexual reproducer, activate as they are laid and trans- was previously supported by the inhibition of egg ferred from the mother into the surrounding water (3). activation by N-(p-amylcinnamoyl) anthranilic acid, By contrast, egg activation is triggered by fertilization in a compound that targets multiple Trp channels (2). organisms such as the mouse and human. Trp channels are notable among ion channels because Although the external signal that triggers egg activation they can be regulated by diverse stimuli (6). Trp channels + differs among species, a wave of elevated intracellular Ca2 change the way they conduct cationic currents across is often the event that initiates the activation signaling plasma membranes in response to various biologic signals + cascade. These Ca2 waves follow a characteristic pattern including changes in temperature, osmolarity, phero- that differs between species; in the oblong eggs from mones, and transduce sensations of touch, pain, and + Drosophila, elevated intracellular Ca2 begins at each taste (7). The vanilloid receptor type 1 Trp channel pole and then travels inward. The wave is propagated (TrpV1) exemplifies this characteristic as it is regulated + by release of intracellular Ca2 signaled by Inositol by heat, acid, voltage, and capsaicin (8). This diverse + 1,4,5-trisphosphate (2). An influx of Ca2 ,however,is complement of signals gives rise to the sensation of heat + required to initiate this wave. A requirement of Ca2 when eating a spicy meal. Notably, various Trp channels entry for egg activation was substantiated by diminished also can be opened by mechanical stimuli (9, 10), thereby + Ca2 waves from eggs incubated in an extracellular suggesting that a Trp channel may mediate Drosophila + + + Ca2 chelator or in the Ca2 channel blocker Gd3 (2). Until egg activation. Indeed, Drosophila ovaries express 3 mem- + now, the molecular identity of the Ca2 -conducting channel, bers of the Trp family: Painless, Trpml, and Trpm (1). or the stimuli that triggered its opening, remained unknown. + Trpm Channels Conduct Ca2 Entry during Stretch Activates Drosophila Eggs Activation A clue for what stimuli may trigger egg activation came To determine whether a Trp channel triggered egg from observing that Drosophila eggs are compressed as activation in Drosophila eggs, Hu and Wolfner independently aDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260 Author contributions: A.E.C. wrote the paper. The author declares no conflict of interest. Published under the PNAS license. See companion article on page 18994. 1Email: [email protected]. Published online August 27, 2019. www.pnas.org/cgi/doi/10.1073/pnas.1913150116 PNAS | September 17, 2019 | vol. 116 | no. 38 | 18757–18758 Downloaded by guest on October 2, 2021 depleted the expression of the 3 candidate channels (1). By imaging A Role for Trpm in Egg Activation May Be Deeply + eggs expressing the fluorescent Ca2 reporter GCaMP, the authors Conserved between Fruit Flies and Mammals demonstrated that only Trpm channels were required for increased Uncovering a required role for Trpm channels in Drosophila egg + intracellular Ca2 evoked by egg activation (1). For these experi- activation reveals common mechanisms used in activation by di- ments, multiple strategies were used to reduce Trpm channel verse eggs (1). The orthologous channel TRPM7 has recently been 2+ expression or conducted currents in D. melanogaster eggs. shown to mediate Ca oscillations during activation of mouse Genetic approaches included germ-line–specific RNA interfer- eggs (11). This suggests that the mechanisms that initiate egg ence knockdown and CRISPR-Cas9 knockout. Application of the activation in fruit flies and mice have been conserved through evolution, a particularly surprising finding because the triggers of Trpm-targeting inhibitor NS8593 was also used. Notably, CRISPR- egg activation are not conserved. However, not all eggs use Trp Cas9–mediated trpm germ-line–specific knockout eggs displayed family channels for egg activation. For example, eggs from the other hallmarks of activation including egg envelope hardening (1). + African clawed frog, Xenopus laevis, rely solely on Ca2 release Moreover, when these eggs were fertilized by wild-type males, they from the endoplasmic reticulum (12), although these eggs do initiated cell cycle resumption. These experimental results were express TrpV4 channels (13). Determining whether Trpm channels also observed in eggs from these transgenic females upon mating are used to activate eggs from common ancestors between – with spermless males. Notably, germ-line specific knockout of Drosophila and mouse will reveal whether the mechanism is trpm resulted in fewer hatched eggs, revealing that the channel conserved but lost in some clades or arose independently. contributes to the maternal support of egg development fol- lowing activation. Together these results resoundingly demon- Acknowledgments 2+ I thank Rachel E. Bainbridge, Kayla M. Komondor, and Maiwase Tembo for strate that Trpm channels are necessary for the Ca wave in critical review of this manuscript. Research in the A.E.C. laboratory is funded by Drosophila egg activation. National Institutes of Health Grant R01GM125638 (to A.E.C.). 1 Q. Hu, M. F. Wolfner, The Drosophila Trpm channel mediates calcium influx during egg activation. Proc. Natl. Acad. Sci. U.S.A. 116, 18994–19000 (2019). 2 V. L. Horner, M. F. Wolfner, Mechanical stimulation by osmotic and hydrostatic pressure activates Drosophila oocytes in vitro in a calcium-dependent manner. Dev. Biol. 316, 100–109 (2008). 3 K. W. Lee, S. E. Webb, A. L. Miller, A wave of free cytosolic calcium traverses zebrafish eggs on activation. Dev. Biol. 214,168–180 (1999). 4 T. Kaneuchi et al., Calcium waves occur as Drosophila oocytes activate. Proc. Natl. Acad. Sci. U.S.A. 112, 791–796 (2015). 5 S. Sukharev, F. Sachs, Molecular force transduction by ion channels: Diversity and unifying principles. J. Cell Sci. 125, 3075–3083 (2012). 6 K. Venkatachalam, C. Montell, TRP channels. Annu. Rev. Biochem. 76, 387–417 (2007). 7 D. E. Clapham, TRP channels as cellular sensors. Nature 426, 517–524 (2003). 8 M. J. Caterina et al., The capsaicin receptor: A heat-activated ion channel in the pain pathway. Nature 389,816–824 (1997). 9 T. Numata, T. Shimizu, Y. Okada, Direct mechano-stress sensitivity of TRPM7 channel. Cell. Physiol. Biochem. 19,1–8 (2007). 10 N. C. Wilkinson, F. Gao, O. P. Hamill, Effects of mechano-gated cation channel blockers on Xenopus oocyte growth and development. J. Membr. Biol. 165, 161–174 (1998). 2+ 11 M. L. Bernhardt et al., TRPM7 and CaV3.2 channels mediate Ca influx required for egg activation at fertilization. Proc. Natl. Acad. Sci. U.S.A. 115, E10370–E10378 (2018). 2+ 12 K. L. Wozniak, M. Tembo, W. A. Phelps, M. T. Lee, A. E. Carlson, PLC and IP3-evoked Ca release initiate the fast block to polyspermy in Xenopus laevis eggs. J. Gen. Physiol. 150, 1239–1248 (2018). 13 K. L. Wozniak, W. A. Phelps, M. Tembo, M. T. Lee, A. E. Carlson, The TMEM16A channel mediates the fast polyspermy block in Xenopus laevis. J. Gen. Physiol. 150, 1249–1259 (2018). 18758 | www.pnas.org/cgi/doi/10.1073/pnas.1913150116 Carlson Downloaded by guest on October 2, 2021.
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