Identification and distribution of a novel platelet-derived growth factor receptor β variant:: Effect of retinoic acid and involvement in cell differentiation

We have shown previously that neonatal testicular gonocytes express platelet-derived growth factor receptors ( PDGFR) alpha and beta. We report the expression of a novel PDGFR beta (V1-PDGFR beta) transcript in gonocytes of 3-d-old rat testes. V1-PDGFR beta nucleotide sequence spans from intron 6 to exon 23 of the PDGFR beta gene, and is predicted to encode a protein lacking part of the extracellular domain. V1-PDGFR beta transcripts are expressed preferentially in developing gonads. The embryonic teratocarcinoma F9 cells, in which differentiation is driven by retinoic acid ( RA), express V1-PDGFR beta, but not wild-type PDGFR beta. Green fluorescent protein-tagged V1-PDGFR beta localized mainly in cytosol of F9, MA-10, and COS-1 cells. FLAG and green fluorescent protein-tagged V1-PDGFR beta displayed tyrosine kinase activities and contain phosphotyrosine residues, suggesting that V1-PDGFR beta is a cytosolic tyrosine kinase. Treatment of F9 cells with RA induced V1-PDGFR beta gene expression, concomitant with changes in morphology and increased mRNA expression of collagen IV and laminin B1, suggesting that V1-PFGR beta is involved in cell differentiation. Similarly, treatment of postnatal d 3 rat gonocytes with RA induced a dose-dependent increase in V1-PDGFR beta expression together with an increase in c-kit and Stra8, markers of more differentiated germ cells and a concomitant decrease in GFR alpha 1, a marker of spermatogonial stem cells. However, an excess of V1-PDGFR beta inhibited RA-mediated collagen IV and laminin B1 expression and altered both RA-dependent and RA-independent morphological changes in F9 cells, while increasing cell survival. These results suggest that the expression of V1-PDGFR beta is tightly regulated during differentiation and that it may play an active role in germ cell differentiation.