Identification of a human homologue of the sea urchin receptor for egg jelly: a polycystic kidney disease-like protein

Abstract

Previous studies have shown sequence similarity between a region of the autosomal dominant polycystic kidney disease (ADPKD) protein, polycystin-1 and a sea urchin sperm glycoprotein involved in fertilization, the receptor for egg jelly (suREJ). We have analysed sequence databases for novel genes encoding PKD/REJ-like proteins and found a significant region of homology to a large open reading frame in genomic sequence from human chromosome 22. Northern analysis showed that this is a functional gene [termed the polycystic kidney disease and receptor for egg jelly related gene ( PKDREJ )], but unlike polycystin-1, has a very restricted expression pattern; the approximately 8 kb transcript was found exclusively in testis, coincident with the timing of sperm maturation. The PKDREJ transcript was cloned by screening a testis cDNA library and RT-PCR which revealed a 7660 bp mRNA terminating with a 900 bp 3'UTR and a polyA tail. Comparison with genomic sequence showed that PKDREJ is intronless; sequencing the mouse orthologue revealed a similar structure. The predicted human PKDREJ protein has 2253 amino acids (calculated molecular mass 255 kDa) and sequence similarity over approximately 2000 amino acids with polycystin-1, corresponding to the predicted membrane associated region and the area of homology ( approximately 1000 amino acids) with the suREJ protein (the REJ module). The suREJ protein binds the glycoprotein coat of the egg (egg jelly), triggering the acrosome reaction, which transforms the sperm into a fusogenic cell. The sequence similarity and expression pattern suggests that PKDREJ is a mammalian equivalent of the suREJ protein and therefore may have a central role in human fertilization.

Genes homologous to the autosomal dominant polycystic kidney disease genes (PKD1 and PKD2)

“…A transcript of approximately 8 kb, corresponding to the expected size, was detected in testis on a northern blot. Consequently, we were able to exclude PKDREJ as a pseudogene, which is consistent with the data described by Hughes et al 38 The N-terminal half of the protein shows homology to the SuREJ protein. The SuREJ protein, which is also homologous to a part of polycystin-1, is involved in triggering the acrosome reaction after binding to the egg jelly.…”

“…These data are in agreement with the expression pattern described by Hughes et al 38 To confirm the mapping of PKDREJ on chromosome 22 we performed a PCR on a whole genome radiation hybrid panel, generating a 900 bp product. A lod score of 14.7 was obtained with marker SHGC-10573 on chromosome band 22q13.3.…”

“…8 In mice, Hughes et al showed expression of PKDREJ in the testis from two weeks after birth to adult life, mirroring the production of mature spermatozoa. 38 These data suggest that PKDREJ is the human homologue of the sea urchin REJ protein, and may be involved in human fertilisation. However, there are several differences.…”

“…Recently, this gene has been described by Hughes et al and designated PKDREJ. 38 Although the homology is not very high, the relationship between this protein and polycystin-1 is…”

“…Here we describe the isolation of one novel gene, PKD2L2, and confirm and extend the findings of two recently published genes, PKD2L 36,37 and PKDREJ. 38 …”