Evidence map›Paper›PMID 22020416›Full record

ArticleJournal of cellular physiology2012

CASK interacts with PMCA4b and JAM-A on the mouse sperm flagellum to regulate Ca2+ homeostasis and motility.

Rolands G Aravindan, Victor P Fomin, Ulhas P Naik, Mark J Modelski, Meghna U Naik, Deni S Galileo, Randall L Duncan, Patricia A Martin-Deleon

Open access · greenAbstract read
In one paragraph

Article in Journal of cellular physiology, 2012. 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
1.3field-weighted citation impact, top 18% 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, 36 citations in OpenAlex.

  1. Article
  2. Review
  3. CaAnimal cells and systems · 2024
    Review
  4. Review
  5. Review
  6. Review
  7. The Roles of Junctional Adhesion Molecules (JAMs) in Cell Migration.Frontiers in cell and developmental biology · 2022
    Review
  8. Article
  9. Acaricidal Mechanism of Scopoletin AgainstFrontiers in physiology · 2019
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

8 authors at 1 institution in 1 country.

Rolands G AravindanDepartment of Biological Sciences, University of Delaware, Newark, DE 19716, USA. pdeleon@udel.edu
Victor P Fomin
Ulhas P Naik
Mark J Modelski
Meghna U Naik
Deni S Galileo
Randall L Duncan
Patricia A Martin-Deleon
University of Delaware · US

Funding

TOWARDS SOLID-STATE NMR STRUCTURES OF GPCRSP20RR015588 · NCRR · UNIVERSITY OF DELAWARE · PI LENHOFF, ABRAHAM M · 2000 to 2009
$18.2M
CHEMISTRY-BIOLOGY INTERFACE PREDOCTORAL TRAININGT32GM008550 · NIGMS · UNIVERSITY OF DELAWARE · PI BAHNSON, BRIAN J · 1994 to 2018
$5.0M
Endogenous suppression of integrin signalingR01HL119374 · NHLBI · UNIVERSITY OF DELAWARE · PI NAIK, ULHAS P · 2013 to 2022
$3.8M
The Role of Acid-active Hyaluronidases in Sperm FunctionR03HD061637 · NICHD · UNIVERSITY OF DELAWARE · PI DELEON, PATRICIA ANASTASIA · 2010 to 2010
$77k
NCRR NIH HHS 5P20RR015588NCRR NIH HHS P20 RR015588NHLBI NIH HHS R01 HL119374NICHD NIH HHS 1R03 HD061637NICHD NIH HHS R03 HD061637NIGMS NIH HHS T32 GM008550
6 · The paper itself

Abstract

Deletion of the highly conserved gene for the major Ca(2+) efflux pump, Plasma membrane calcium/calmodulin-dependent ATPase 4b (Pmca4b), in the mouse leads to loss of progressive and hyperactivated sperm motility and infertility. Here we first demonstrate that compared to wild-type (WT), Junctional adhesion molecule-A (Jam-A) null sperm, previously shown to have motility defects and an abnormal mitochondrial phenotype reminiscent of that seen in Pmca4b nulls, exhibit reduced (P < 0.001) ATP levels, significantly (P < 0.001) greater cytosolic Ca(2+) concentration ([Ca(2+) ](c)) and ∼10-fold higher mitochondrial sequestration, indicating Ca(2+) overload. Investigating the mechanism involved, we used co-immunoprecipitation studies to show that CASK (Ca(2+) /calmodulin-dependent serine kinase), identified for the first time on the sperm flagellum where it co-localizes with both PMCA4b and JAM-A on the proximal principal piece, acts as a common interacting partner of both. Importantly, CASK binds alternatively and non-synergistically with each of these molecules via its single PDZ (PDS-95/Dlg/ZO-1) domain to either inhibit or promote efflux. In the absence of CASK-JAM-A interaction in Jam-A null sperm, CASK-PMCA4b interaction is increased, resulting in inhibition of PMCA4b's enzymatic activity, consequent Ca(2+) accumulation, and a ∼6-fold over-expression of constitutively ATP-utilizing CASK, compared to WT. Thus, CASK negatively regulates PMCA4b by directly binding to it and JAM-A positively regulates it indirectly through CASK. The decreased motility is likely due to the collateral net deficit in ATP observed in nulls. Our data indicate that Ca(2+) homeostasis in sperm is maintained by the relative ratios of CASK-PMCA4b and CASK-JAM-A interactions.

Indexed as

Adenosine TriphosphateAnimalsCalciumCalcium ChannelsCell Adhesion MoleculesGene Expression RegulationGuanylate KinasesInfertilityMaleMembrane Potential, MitochondrialMiceMice, Inbred C57BLPlasma Membrane Calcium-Transporting ATPasesReceptors, Cell SurfaceSingle-Cell AnalysisSpermatozoaAdenosine TriphosphateCalciumCalcium ChannelsCASK kinasesCatsper1 protein, mouseCell Adhesion MoleculesF11r protein, mouseGuanylate KinasesPlasma Membrane Calcium-Transporting ATPasesReceptors, Cell Surface

Identifiers

PMID22020416
PMCPMC3383836
OpenAlexW2016414410

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.