Evidence map›Paper›PMID 26060254›Full record

ArticleThe Journal of biological chemistry2015

Src Kinase Is the Connecting Player between Protein Kinase A (PKA) Activation and Hyperpolarization through SLO3 Potassium Channel Regulation in Mouse Sperm.

Cintia Stival, Florenza A La Spina, Carolina Baró Graf, Enid Arcelay, Silvia E Arranz, Juan J Ferreira, Sibylle Le Grand, Victor A Dzikunu, Celia M Santi, Pablo E Visconti and 2 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
5.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 43 citations in OpenAlex.

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  19. Molecular Basis of Human Sperm Capacitation.Frontiers in cell and developmental biology · 2018
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Cintia StivalFrom the Instituto de Biología Molecular y Celular de Rosario, CONICET-UNR, and Laboratorio de Especialidades Reproductivas, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario SF2000, Argentina.
Florenza A La Spinathe Instituto de Biología y Medicina Experimental, CONICET, Ciudad Autónoma de Buenos Aires C1428ADN, Argentina.
Carolina Baró GrafFrom the Instituto de Biología Molecular y Celular de Rosario, CONICET-UNR, and Laboratorio de Especialidades Reproductivas, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario SF2000, Argentina.
Enid Arcelaythe Department of Veterinary and Animal Science, Paige Labs, University of Massachusetts, Amherst, Massachusetts 01003.
Silvia E ArranzFrom the Instituto de Biología Molecular y Celular de Rosario, CONICET-UNR, and Laboratorio de Especialidades Reproductivas, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario SF2000, Argentina.
Juan J Ferreirathe Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis Missouri 63110, and.
Sibylle Le Grandthe Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis Missouri 63110, and.
Victor A Dzikunuthe Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis Missouri 63110, and.
Celia M Santithe Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis Missouri 63110, and.
Pablo E Viscontithe Department of Veterinary and Animal Science, Paige Labs, University of Massachusetts, Amherst, Massachusetts 01003.
Mariano G Buffonethe Instituto de Biología y Medicina Experimental, CONICET, Ciudad Autónoma de Buenos Aires C1428ADN, Argentina.
Dario KrapfFrom the Instituto de Biología Molecular y Celular de Rosario, CONICET-UNR, and Laboratorio de Especialidades Reproductivas, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario SF2000, Argentina, krapf@ibr-conicet.gov.ar.
Washington University in St. Louis · USExperimental Medicine and Biology Institute · AR

Funding

Sperm Ca2+ Signaling and Energy Pathways in basic science and ARTR01HD038082 · NICHD · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI VISCONTI, PABLO E. · 2000 to 2025
$6.5M
SLO3 KO MOUSE: A TOOL TO REVEAL VOLTAGE-DEPENDENT PROCESSES IN SPERM FERTILITYR01HD069631 · NICHD · WASHINGTON UNIVERSITY · PI SANTI, CELIA M · 2011 to 2022
$3.3M
Phosphorylation Events During Sperm CapacitationR01HD044044 · NICHD · UNIVERSITY OF MASSACHUSETTS AMHERST · PI VISCONTI, PABLO E. · 2005 to 2015
$2.8M
ROLE OF ACTIN CYTOSKELETON DURING MOUSE SPERM ACROSOMAL EXOCYTOSISR01TW008662 · FIC · FUND INST BIOL Y MED EXPERIMENTAL · PI BUFFONE, MARIANO G · 2012 to 2016
$262k
FIC NIH HHS R01 TW008662FIC NIH HHS R01TW008662NICHD NIH HHS HD440044NICHD NIH HHS R01 HD038082NICHD NIH HHS R01 HD044044NICHD NIH HHS R01 HD069631NICHD NIH HHS R01 HD38082
6 · The paper itself

Abstract

Plasma membrane hyperpolarization is crucial for mammalian sperm to acquire acrosomal responsiveness during capacitation. Among the signaling events leading to mammalian sperm capacitation, the immediate activation of protein kinase A plays a pivotal role, promoting the subsequent stimulation of protein tyrosine phosphorylation that associates with fertilizing capacity. We have shown previously that mice deficient in the tyrosine kinase cSrc are infertile and exhibit improper cauda epididymis development. It is therefore not clear whether lack of sperm functionality is due to problems in epididymal maturation or to the absence of cSrc in sperm. To further address this problem, we investigated the kinetics of cSrc activation using anti-Tyr(P)-416-cSrc antibodies that only recognize active cSrc. Our results provide evidence that cSrc is activated downstream of PKA and that inhibition of its activity blocks the capacitation-induced hyperpolarization of the sperm plasma membrane without blocking the increase in tyrosine phosphorylation that accompanies capacitation. In addition, we show that cSrc inhibition also blocks the agonist-induced acrosome reaction and that this inhibition is overcome by pharmacological hyperpolarization. Considering that capacitation-induced hyperpolarization is mediated by SLO3, we evaluated the action of cSrc inhibitors on the heterologously expressed SLO3 channel. Our results indicate that, similar to SLO1 K(+) channels, cSrc blockers significantly decreased SLO3-mediated currents. Together, these results are consistent with findings showing that hyperpolarization of the sperm plasma membrane is necessary and sufficient to prepare the sperm for the acrosome reaction and suggest that changes in sperm membrane potential are mediated by cSrc activation.

Indexed as

AcrosomeAnimalsCell MembraneCell PolarityCyclic AMPCyclic AMP-Dependent Protein KinasesGene Expression RegulationHumansLarge-Conductance Calcium-Activated Potassium ChannelsMaleMembrane PotentialsMiceSignal TransductionSpermatozoaSperm Capacitationsrc-Family KinasesCyclic AMPCyclic AMP-Dependent Protein KinasesKcnu1 protein, mouseLarge-Conductance Calcium-Activated Potassium Channelssrc-Family Kinasesacrosome reactionmembrane potentialphosphotyrosine signalingPKApotassium channelspermSrc

Identifiers

PMID26060254
PMCPMC4513139
OpenAlexW1601331762

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.