CRIS—A Novel cAMP-Binding Protein Controlling Spermiogenesis and the Development of Flagellar Bending

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 Ca2+ 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 Ca2+-regulated proteins that—in mature sperm—are involved in flagellar bending.

Direct action of endocrine disrupting chemicals on human sperm

“…Human and mouse sperm were prepared as described [2,38]; changes in [Ca 2+ ] i and pH i were measured in human sperm loaded with the Ca 2+ indicator Fluo-4 and the pH i indicator BCECF, respectively, in 384-microtiter plates in a fluorescence plate reader (Fluostar Omega, BMG Labtech, Germany) at 30°C [2,13]. Mouse sperm were loaded with the Ca 2+ indicator Cal-520 (5 lM) (ATT Bioquest, USA) and changes in [Ca 2+ ] i were measured in a rapid-mixing device (SFM-400; Biologic, France) in the stopped-flow mode [38]. Whole-cell recordings were performed as described [2,13].…”

Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development

“…The signal transduction process mediated by cAMP second messengers is initiated by binding of the ligand to various cAMP sensors (FIGURE 1). In mammals, at least five families of cAMP effector proteins are known: the classic protein kinase A (PKA) (1020), the cyclic nucleotide regulated ion channels (CNG and HCN) (1219), the exchange proteins directly activated by cAMP (EPAC1 and EPAC2) (229,510), the Popeye domain containing (POPDC) proteins (913), and the cyclic nucleotide receptor involved in sperm function (CRIS) (556). Despite their diverse functionalities, these cAMP effectors all share a common cyclic nucleotide binding (CNB) domain that is evolutionary conserved with an ancient ancestor: the bacterial cAMP receptor protein (CRP) (496).…”

Central role of soluble adenylyl cyclase and cAMP in sperm physiology

“…Finally, a novel CNBD containing protein named CRIS (for cyclic nucleotide receptor involved in sperm function) has been recently identified 154 . CRIS is exclusively expressed in testicular germ cells while it is not present in mature sperm.…”