CRIS-a novel cAMP-binding protein controlling spermiogenesis and the development of flagellar bending

Anke Miriam Krähling; Luis Alvarez; Katharina Debowski; Qui Van; Monika Gunkel; Stephan Irsen; Ashraf Al-Amoudi; Timo Strünker; Elisabeth Kremmer; Eberhard Krause; Ingo Voigt; Simone Wörtge; Ari Waisman; Ingo Weyand; Reinhard Seifert; Ulrich Benjamin Kaupp; Dagmar Wachten

doi:10.1371/journal.pgen.1003960

CRIS-a novel cAMP-binding protein controlling spermiogenesis and the development of flagellar bending

PLoS Genet. 2013;9(12):e1003960. doi: 10.1371/journal.pgen.1003960. Epub 2013 Dec 5.

Authors

Anke Miriam Krähling¹, Luis Alvarez, Katharina Debowski, Qui Van, Monika Gunkel, Stephan Irsen, Ashraf Al-Amoudi, Timo Strünker, Elisabeth Kremmer, Eberhard Krause, Ingo Voigt, Simone Wörtge, Ari Waisman, Ingo Weyand, Reinhard Seifert, Ulrich Benjamin Kaupp, Dagmar Wachten

Affiliation

¹ Center of Advanced European Studies and Research (caesar), Department of Molecular Sensory Systems, Bonn, Germany.

Abstract

The second messengers cAMP and cGMP activate their target proteins by binding to a conserved cyclic nucleotide-binding domain (CNBD). Here, we identify and characterize an entirely novel CNBD-containing protein called CRIS (cyclic nucleotide receptor involved in sperm function) that is unrelated to any of the other members of this protein family. CRIS is exclusively expressed in sperm precursor cells. Cris-deficient male mice are either infertile due to a lack of sperm resulting from spermatogenic arrest, or subfertile due to impaired sperm motility. The motility defect is caused by altered Ca(2+) regulation of flagellar beat asymmetry, leading to a beating pattern that is reminiscent of sperm hyperactivation. Our results suggest that CRIS interacts during spermiogenesis with Ca(2+)-regulated proteins that--in mature sperm--are involved in flagellar bending.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium / metabolism
Carrier Proteins / genetics*
Cyclic AMP / genetics*
Cyclic AMP / metabolism
Cyclic GMP / metabolism
Flagella / genetics*
Flagella / metabolism
Humans
Intracellular Signaling Peptides and Proteins
Male
Mice
Phosphorylation
Protein Binding / genetics*
Signal Transduction / genetics
Sperm Motility / genetics
Spermatogenesis / genetics*
Spermatozoa / metabolism

Substances

CRIS protein, mouse
Carrier Proteins
Intracellular Signaling Peptides and Proteins
Cyclic AMP
Cyclic GMP
Calcium

Grants and funding

This work was supported by the German Research Foundation (SFB645; DW and UBK are members of the ImmunoSensation Cluster of Excellence). DW was funded by a fellowship from the Boehringer Ingelheim Fonds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.