Cysteine‐rich secretory proteins are not exclusively expressed in the male reproductive tract

Abstract

The Cysteine-RIch Secretory Proteins (CRISPs) are abundantly produced in the male reproductive tract of mammals and within the venom of reptiles and have been shown to regulate ion channel activity. CRISPs, along with the Antigen-5 proteins and the Pathogenesis related-1 (Pr-1) proteins, form the CAP superfamily of proteins. Analyses of EST expression databases are increasingly suggesting that mammalian CRISPs are expressed more widely than in the reproductive tract. We, therefore, conducted a reverse transcription PCR expression profile and immunohistochemical analyses of 16 mouse tissues to define the sites of production of each of the four murine CRISPs. These data showed that each of the CRISPs have distinct and sometimes overlapping expression profiles, typically associated with the male and female reproductive tract, the secretory epithelia of exocrine glands, and immune tissues including the spleen and thymus. These investigations raise the potential for a role for CRISPs in general mammalian physiology. Developmental Dynamics 237:3313-3323, 2008.

Cysteine-rich secretory protein 4 is an inhibitor of transient receptor potential M8 with a role in establishing sperm function

“…S7), indicating that the phenotype was a result of the absence of CRISP4 rather than altered TRPM8 processing. Discussion CRISP4 is produced in the proximal regions of the epididymis, where it surrounds the transcriptionally silent sperm throughout epididymal transit (7,8,33). Herein, we have confirmed the presence of functional TRPM8 on mouse sperm and identified CRISP4 as a physiologically relevant inhibitor of TRPM8 activity using both in vitro and in vivo methods.…”

“…The mechanism by which TRPM8 activity is regulated in these tissues remains to be fully determined; however, several regulatory mediators have been identified, including Ca 2+ , pH, PIP2 and phosphorylation (43)(44)(45)(46)(47). In those tissues where CRISP4 and TRPM8 are coexpressed (33), our data suggests that CRISP4 is also likely to modulate TRPM8 function.…”

“…Although this is undoubtedly the case in the epididymal lumen, this conclusion cannot immediately be drawn for other tissues where CRISP4 has been demonstrated, namely skeletal muscle, spleen, thymus, and lacrimal glands (7,8,33). Supporting the possibility of a functionally relevant role for CRISP4 within these tissues, however, it has recently been shown that the full-length venom CRISP PsTx has at least a 120-fold higher activity against cyclic-nucleotide gated A2 in comparison with its ICR region alone (CRISP domain), indicating a dramatic enhancement of activity because of the presence of both domains.…”

“…Crisp4 cDNA was amplified from the mouse epididymis and the CRISP4 CRISP domain expressed and purified as described previously (10) (SI Materials and Methods). Full-length recombinant CRISP1 to -4 was produced as described and was insoluble (33).…”

“…Deregulated ion channel expression/function is associated with many diseases (50,51) and ion channels are a major class of therapeutic drug target (52). As such, the characterization of endogenous protein ion channel regulators with expression beyond the reproductive tract is of broad significance (33).…”