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12 Article Chronology: 13 Received 30 August 2006 14 Revised version received 15 26 December 2006 16 Accepted 23 January 2007 7 The coxsackie and adenovirus receptor (CAR), a putative cell–cell adhesion molecule, has 8 attracted wide interest due to its importance in viral pathogenesis and in mediating 9 adenoviral gene delivery. However, the distribution pattern and physiological function of 20 CAR in the testis is still not clear. Here, we identified CAR in Sertoli cells and germ cells of 21 rats. In vivo studies have shown that CAR resides at the blood–testis barrier as well as at 22 the ectoplasmic specialization. The persistent expression of CAR in rat testes from 23 neonatal period throughout adulthood implicates its role in spermatogenesis. Using 24 primary Sertoli cell cultures, we observed a significant induction of CAR during the 25 formation of Sertoli cell epithelium. Furthermore, CAR was seen to be concentrated at 26 inter-Sertoli cell junctions, co-localizing with tight junction protein marker ZO-1 and 27 adherens junction protein N-cadherin. CAR was also found to be associated with proteins 28 of Src kinase family and its protein level declined after TNFα treatment in Sertoli cell 29 cultures. Immunofluorescent staining of isolated germ cells has revealed the presence of 30 CAR on spermatogonia, spermatocytes, round spermatids and elongate spermatids. Taken 31 together, we propose that CAR functions as an adhesion molecule in maintaining the 32 inter-Sertoli cell junctions at the basal compartment of the seminiferous epithelium. In 33 addition, CAR may confer adhesion between Sertoli and germ cells at the Sertoli–germ cell 34 interface. It is possible that the receptor utilized by viral pathogens to breakthrough the 35 epithelial barrier was also employed by developing germ cells to migrate through the 36 inter-Sertoli cell junctions. 37 © 2007 Published by Elsevier Inc. 38