Sperm Epidermal Growth Factor Receptor (EGFR) Mediates α7 Acetylcholine Receptor (AChR) Activation to Promote Fertilization

Jaldety, Yael; Glick, Yaïr; Orr-Urtreger, Avi; Ickowicz, Debby; Gerber, Doron; Breitbart, Haim

doi:10.1074/jbc.m111.292292

Cited by 23 publications

(17 citation statements)

References 71 publications

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“…Choline is also an efficacious agonist of α7, which further extends the spatial range of cholinergic transmission. This combination of volume transmission and extension of bioactivity by choline is also relevant in nonneuronal cells, such as lymphocytes and macrophages, where α7 is involved in anti-inflammatory responses (15,16), and in sperm cells where α7 has a role in fertilization (17).…”

mentioning

confidence: 99%

Stoichiometry for activation of neuronal α7 nicotinic receptors

Andersen

Corradi

Sine

et al. 2013

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

118

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Neuronal α7 nicotinic receptors elicit rapid cation influx in response to acetylcholine (ACh) or its hydrolysis product choline. They contribute to cognition, synaptic plasticity, and neuroprotection and have been implicated in neurodegenerative and neuropsychiatric disorders. α7, however, often localizes distal to sites of nerve-released ACh and binds ACh with low affinity, and thus elicits its biological response with low agonist occupancy. To assess the function of α7 when ACh occupies fewer than five of its identical binding sites, we measured the open-channel lifetime of individual receptors in which four of the five ACh binding sites were disabled. To improve the time resolution of the inherently brief α7 channel openings, background mutations or a potentiator was used to increase open duration. We find that, in receptors with only one intact binding site, the open-channel lifetime is indistinguishable from receptors with five intact binding sites, counter to expectations from prototypical neurotransmitter-gated ion channels where the open-channel lifetime increases with the number of binding sites occupied by agonist. Replacing the membrane-embedded domain of α7 by that of the related 5-HT 3 A receptor increases the number of sites that need to be occupied to achieve the maximal open-channel lifetime, thus revealing a unique interdependence between the detector and actuator domains of these receptors. The distinctive ability of a single occupancy to elicit a full biological response adapts α7 to volume transmission, a prevalent mechanism of ACh-mediated signaling in the nervous system and nonneuronal cells.Cys-loop receptors | α7 nicotinic receptor | patch-clamp | agonist binding site | channel gating

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mentioning

confidence: 99%

Stoichiometry for activation of neuronal α7 nicotinic receptors

Andersen

Corradi

Sine

et al. 2013

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

118

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“…Interestingly, α7nAChR ligands like PNU282987 and acetylcholine stimulate the AR in mouse sperm at micromolar concentrations. Moreover, nM concentrations of some antagonists of nAChR such as α-bungarotoxin, α-conotoxin, and methyllycaconitine inhibited the AR initiated by acetylcholine or ZP (Son and Meizel 2003;Jaldety et al 2012). Furthermore, the synergistic effect between ZP, ACh, and PNU282987 on the AR further supported a possible cooperation between α7nAChR and ZP, suggesting that the two pathways are not redundant (Jaldety et al 2012).…”

Section: Acetylcholine Receptorsmentioning

confidence: 98%

“…Moreover, nM concentrations of some antagonists of nAChR such as α-bungarotoxin, α-conotoxin, and methyllycaconitine inhibited the AR initiated by acetylcholine or ZP (Son and Meizel 2003;Jaldety et al 2012). Furthermore, the synergistic effect between ZP, ACh, and PNU282987 on the AR further supported a possible cooperation between α7nAChR and ZP, suggesting that the two pathways are not redundant (Jaldety et al 2012). The effect of these nAChR antagonists did not block the AR initiated by Ca 2+ ionophore A23187, suggesting that the role of α7nAChR is upstream of Ca 2+ influx (Son and Meizel 2003).…”

Section: Acetylcholine Receptorsmentioning

confidence: 98%

Role of Ion Channels in the Sperm Acrosome Reaction

Beltrán

Treviño

Mata-Martínez

et al. 2016

Advances in Anatomy, Embryology and Cell Biology

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The acrosome reaction (AR) is a unique exocytotic process where the acrosome, a single membrane-delimited specialized organelle, overlying the nucleus in the sperm head of many species, fuses with the overlying plasma membrane. This reaction, triggered by physiological inducers from the female gamete, its vicinity, or other stimuli, discharges the acrosomal content modifying the plasma membrane, incorporating the inner acrosomal membrane, and exposing it to the extracellular medium. The AR is essential for sperm-egg coat penetration, fusion with the eggs' plasma membrane, and fertilization. As in most exocytotic processes Ca(2+) is crucial for the AR, as well as intracellular pH and membrane potential changes. Thus, among the required processes needed for this reaction, ion permeability changes involving channels are pivotal. In spite of the key role ion channels play in the AR, their identity and regulation is not fully understood. Though molecular and pharmacological evidence indicates that various ionic channels participate during the AR, such as store-operated Ca(2+) channels and voltage-dependent Ca(2+) channels, whole cell patch clamp recordings have failed to detect some of them until now. Since sperm display a very high resistance and a minute cytoplasmic volume, very few channels are needed to achieve large membrane potential and concentration changes. Functional detection of few channels in the morphologically complex and tiny sperm poses technical problems, especially when their conductance is very small, as in the case of SOCs. Single channel recordings and novel fluorescence microscopy strategies will help to define the participation of ionic channels in the intertwined signaling network that orchestrates the AR.

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“…Also several reports suggest that nACh receptors (α7 nicotinic acetylcholine receptor) are present in mammalian sperm which is involved in the zona pellucidainduced acrosome reaction along with increased intracellular calcium levels [19] . As well known, organophosphorus compounds (OPs) and carbamates bind to an active site of acetylcholinesterase (AChE) and inhibit the functionality of this enzyme.…”

Section: Discussionmentioning

confidence: 99%

Bazı Pestisitlerin Teke ve Köpek Sperması Üzerine İn Vitro Toksisiteleri

Yurdakök-Dikmen¹,

Tekin²,

Tirpan³

et al. 2017

Kafkas Univ Vet Fak Derg

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Citation of This AbstractIn vitro toxic effects of selected pesticides (cypermethrin, flumethrin, propoxur, carbaryl, chlorpyrifos, metamidophos) were evaluated on dog and buck fresh spermatozoa using MTT (mitochondrial activity/viability), NeutralRed-NR (lysosomal activity/viability) and CASA (motility parameters/VCL, VSL, VAP, linearity, straightness, wobble) tests. For buck, the most toxic compounds were carbamates followed by organophosphate and pyrethroids. Carbamates, again induced the highest toxicity in dog sperm, followed by pyrethroids. In general, all pesticide treatments were found to increase the hyperactivity of buck spermatozoa except flumethrin; whereas a decrease was present for dog spermatozoa (except carbaryl). A decrease of VCL, VSL and VAP parameters was evident in buck (P<0.05), whereas no difference was found in dog sperm (P>0.05). Overall, flumethrin was found to induce less effect on motility parameters compared to cypermethrin. As a conclusion, the combination of MTT and CASA along with NR would provide more accurate data for the in vitro evaluation of chemicals on spermatozoa; where alternative testing strategies for the ReproTox tests (especially for cosmetic product safety assessment where animal testing is banned) are recommended nowadays with battery strategies and species specific differences would play a key role for understanding the defense mechanisms. Keywords: Pesticides, Buck spermatozoa, Dog spermatozoa, In vitro toxicity, MTT, CASA, Neutral red Bazı Pestisitlerin Teke ve Köpek Sperması Üzerine İn Vitro Toksisiteleri ÖzetBu çalışmada, bazı pestisitlerin (sipermetrin, flumetrin, propoksur, karbaril, klorprifos, metamidofos) köpek ve teke taze spermaları üzerindeki etkileri, MTT (mitokondriyal etkinlik/canlılık), Nötral Kırmızı-NK (lizozomal etkinlik/canlılık) ve Bilgisayar Destekli Semen Analizi-CASA (motilite parametreleri, VCL, VSL, VAP, lineerlik, doğrusallık, yalpalama) kullanılarak in vitro olarak araştırıldı. Teke sperması üzerine canlılık ve motilite bakımından en toksik bileşiğin karbamatlar, ardından organofosfatlar ve piretroitler olduğu; köpek spermasında ise aynı şekilde karbamatların, ardından da piretroitlerin toksik etki gösterdiği tespit edildi. Genel olarak tüm pestisit uygulamalarının teke spermasında hiperaktiviteyi (flumetrin dışında) arttırdığı, köpek spermasında ise azalttığı tespit edildi (karbaril dışında). Tekede VCL, VSL ve VAP parametrelerinde azalma gözlenirken (P<0.05), köpek spermasında anlamlı bir fark gözlenmedi (P>0.05). Piretroitler arasında flumetrinin, motilite parametreleri üzerine etkisi sipermetrine göre daha az bulundu. Sonuç olarak üreme toksisite testlerinde (özellikle kozmetik ürünlerin toksisite testlerinde hayvan deneylerinin yasaklandığı göz önünde bulundurularak) alternatif testler arasında bulunan ve batarya testleri içerisinde yer alan in vitro sperm toksisite araştırmalarında; MTT ve CASA ile birlikte NK'nın birlikte kullanılmasının kimyasalların sperma üzerine etkilerinin değerlendirilmesinde daha etkili olacağı ve türe özgü...

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Sperm Epidermal Growth Factor Receptor (EGFR) Mediates α7 Acetylcholine Receptor (AChR) Activation to Promote Fertilization

Cited by 23 publications

References 71 publications

Stoichiometry for activation of neuronal α7 nicotinic receptors

Stoichiometry for activation of neuronal α7 nicotinic receptors

Role of Ion Channels in the Sperm Acrosome Reaction

Bazı Pestisitlerin Teke ve Köpek Sperması Üzerine İn Vitro Toksisiteleri

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