Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2010 Jun 18;28525:19259-66. doi: 10.1074/jbc.M109.100156.
Show Gene links
Show Anatomy links
Phosphatidylinositol 4,5-bisphosphate activates Slo3 currents and its hydrolysis underlies the epidermal growth factor-induced current inhibition.
Tang QY
,
Zhang Z
,
Xia J
,
Ren D
,
Logothetis DE
.
???displayArticle.abstract???
The Slo3 gene encodes a high conductance potassium channel, which is activated by both voltage and intracellular alkalinization. Slo3 is specifically expressed in mammalian sperm cells, where it gives rise to pH-dependent outwardly rectifying K(+) currents. Sperm Slo3 is the main current responsible for the capacitation-induced hyperpolarization, which is required for the ensuing acrosome reaction, an exocytotic process essential for fertilization. Here we show that in intact spermatozoa and in a heterologous expression system, the activation of Slo3 currents is regulated by phosphatidylinositol 4,5-bisphosphate (PIP(2)). Depletion of endogenous PIP(2) in inside-out macropatches from Xenopus oocytes inhibited heterologously expressed Slo3 currents. Whole-cell recordings of sperm Slo3 currents or of Slo3 channels co-expressed in Xenopus oocytes with epidermal growth factor receptor, demonstrated that stimulation by epidermal growth factor (EGF) could inhibit channel activity in a PIP(2)-dependent manner. High concentrations of PIP(2) in the patch pipette not only resulted in a strong increase in sperm Slo3 current density but also prevented the EGF-induced inhibition of this current. Mutation of positively charged residues involved in channel-PIP(2) interactions enhanced the EGF-induced inhibition of Slo3 currents. Overall, our results suggest that PIP(2) is an important regulator for Slo3 activation and that receptor-mediated hydrolysis of PIP(2) leads to inhibition of Slo3 currents both in native and heterologous expression systems.
Arbuzova,
Fluorescently labeled neomycin as a probe of phosphatidylinositol-4, 5-bisphosphate in membranes.
2000, Pubmed
Arbuzova,
Fluorescently labeled neomycin as a probe of phosphatidylinositol-4, 5-bisphosphate in membranes.
2000,
Pubmed
Atkinson,
A component of calcium-activated potassium channels encoded by the Drosophila slo locus.
1991,
Pubmed
Breitbart,
Signaling pathways in sperm capacitation and acrosome reaction.
2003,
Pubmed
Darszon,
Sperm channel diversity and functional multiplicity.
2006,
Pubmed
Fan,
Anionic phospholipids activate ATP-sensitive potassium channels.
1997,
Pubmed
Fujita,
Ropporin, a sperm-specific binding protein of rhophilin, that is localized in the fibrous sheath of sperm flagella.
2000,
Pubmed
Furuya,
[Effect of epidermal growth factor (EGF) on mouse sperm capacitation].
1993,
Pubmed
Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed
Huang,
Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma.
1998,
Pubmed
,
Xenbase
Jungnickel,
Phosphoinositide-dependent pathways in mouse sperm are regulated by egg ZP3 and drive the acrosome reaction.
2007,
Pubmed
Kavran,
Specificity and promiscuity in phosphoinositide binding by pleckstrin homology domains.
1998,
Pubmed
Kirichok,
Whole-cell patch-clamp measurements of spermatozoa reveal an alkaline-activated Ca2+ channel.
2006,
Pubmed
Kobrinsky,
Receptor-mediated hydrolysis of plasma membrane messenger PIP2 leads to K+-current desensitization.
2000,
Pubmed
,
Xenbase
Lax,
Epidermal growth factor induces acrosomal exocytosis in bovine sperm.
1994,
Pubmed
Liu,
CatSperbeta, a novel transmembrane protein in the CatSper channel complex.
2007,
Pubmed
Logothetis,
Channelopathies linked to plasma membrane phosphoinositides.
2010,
Pubmed
Logothetis,
Incremental reductions of positive charge within the S4 region of a voltage-gated K+ channel result in corresponding decreases in gating charge.
1992,
Pubmed
,
Xenbase
Logothetis,
Phosphoinositide-mediated gating of inwardly rectifying K(+) channels.
2007,
Pubmed
Lopes,
Protein kinase A modulates PLC-dependent regulation and PIP2-sensitivity of K+ channels.
2007,
Pubmed
,
Xenbase
Lopes,
Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies.
2002,
Pubmed
,
Xenbase
Margolis,
EGF induces tyrosine phosphorylation of phospholipase C-II: a potential mechanism for EGF receptor signaling.
1989,
Pubmed
Martínez-López,
Mouse sperm K+ currents stimulated by pH and cAMP possibly coded by Slo3 channels.
2009,
Pubmed
,
Xenbase
Murase,
Epidermal growth factor stimulates hydrolysis of phosphatidylinositol 4,5-bisphosphate, generation of diacylglycerol and exocytosis in mouse spermatozoa.
1995,
Pubmed
NagDas,
Identification of ras and its downstream signaling elements and their potential role in hamster sperm motility.
2002,
Pubmed
Nakanishi,
A wortmannin-sensitive phosphatidylinositol 4-kinase that regulates hormone-sensitive pools of inositolphospholipids.
1995,
Pubmed
Navarro,
Ion channels that control fertility in mammalian spermatozoa.
2008,
Pubmed
Navarro,
KSper, a pH-sensitive K+ current that controls sperm membrane potential.
2007,
Pubmed
Oliva-Hernández,
Localization of the epidermal growth factor (EGF) in the epididymis and accessory genital glands of the boar and functional effects on spermatozoa.
2008,
Pubmed
Rapedius,
H bonding at the helix-bundle crossing controls gating in Kir potassium channels.
2007,
Pubmed
,
Xenbase
Ravichandran,
Evidence for a requirement for both phospholipid and phosphotyrosine binding via the Shc phosphotyrosine-binding domain in vivo.
1997,
Pubmed
Rohács,
PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain.
2005,
Pubmed
Rohács,
Specificity of activation by phosphoinositides determines lipid regulation of Kir channels.
2003,
Pubmed
,
Xenbase
Rosenhouse-Dantsker,
Potassium channel gating in the absence of the highly conserved glycine of the inner transmembrane helix.
2007,
Pubmed
,
Xenbase
Saito,
A cysteine-rich domain defined by a novel exon in a slo variant in rat adrenal chromaffin cells and PC12 cells.
1997,
Pubmed
,
Xenbase
Salkoff,
High-conductance potassium channels of the SLO family.
2006,
Pubmed
Santi,
The SLO3 sperm-specific potassium channel plays a vital role in male fertility.
2010,
Pubmed
Schreiber,
Slo3, a novel pH-sensitive K+ channel from mammalian spermatocytes.
1998,
Pubmed
Schulze,
Phosphatidylinositol 4,5-bisphosphate (PIP2) modulation of ATP and pH sensitivity in Kir channels. A tale of an active and a silent PIP2 site in the N terminus.
2003,
Pubmed
Shyng,
Structural determinants of PIP(2) regulation of inward rectifier K(ATP) channels.
2000,
Pubmed
Suh,
Regulation of ion channels by phosphatidylinositol 4,5-bisphosphate.
2005,
Pubmed
Suh,
PIP2 is a necessary cofactor for ion channel function: how and why?
2008,
Pubmed
Tang,
Block of mouse Slo1 and Slo3 K+ channels by CTX, IbTX, TEA, 4-AP and quinidine.
2010,
Pubmed
,
Xenbase
Tang,
Characterization of a functionally expressed stretch-activated BKca channel cloned from chick ventricular myocytes.
2003,
Pubmed
Vaithianathan,
Direct regulation of BK channels by phosphatidylinositol 4,5-bisphosphate as a novel signaling pathway.
2008,
Pubmed
,
Xenbase
Visconti,
Novel signaling pathways involved in sperm acquisition of fertilizing capacity.
2002,
Pubmed
Xia,
CATSPER channel-mediated Ca2+ entry into mouse sperm triggers a tail-to-head propagation.
2007,
Pubmed
Xie,
Long polyamines act as cofactors in PIP2 activation of inward rectifier potassium (Kir2.1) channels.
2005,
Pubmed
,
Xenbase
Xie,
Activation of inwardly rectifying potassium (Kir) channels by phosphatidylinosital-4,5-bisphosphate (PIP2): interaction with other regulatory ligands.
2007,
Pubmed
Yang,
Interactions between beta subunits of the KCNMB family and Slo3: beta4 selectively modulates Slo3 expression and function.
2009,
Pubmed
,
Xenbase
Zhang,
pH-regulated Slo3 K+ channels: properties of unitary currents.
2006,
Pubmed
,
Xenbase
Zhang,
Sperm ion channels: molecular targets for the next generation of contraceptive medicines?
2005,
Pubmed
Zhang,
PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents.
2003,
Pubmed
,
Xenbase
Zhang,
Activation of inwardly rectifying K+ channels by distinct PtdIns(4,5)P2 interactions.
1999,
Pubmed
,
Xenbase
Zhang,
Slo3 K+ channels: voltage and pH dependence of macroscopic currents.
2006,
Pubmed
,
Xenbase
