The coxsackievirus-adenovirus receptor protein as a cell adhesion moleculein the developing mouse brain

In an attempt to elucidate the molecular mechanisms underlying neuro-networ k formation in the developing brain, we analyzed 130 proteolytic cleavage p eptides of membrane proteins purified from newborn mouse brains. We describ e here the characterization of a membrane protein with an apparent molecula r mass of 46 kDa, a member of the immunoglobulin superfamily of which the c DNA sequence was recently reported, encoding the mouse homologue of the hum an coxsackievirus and adenovirus receptor (mCAR). Western and Northern blot analyses demonstrated the abundant expression of mCAR in the mouse brain, the highest level being observed in the newborn mouse brain, and its expres sion was detected in embryos as early as at 10.5 days post-coitus (dpc), bu t decreased rapidly after birth. On in situ hybridization, mCAR mRNA expres sion was observed throughout the newborn mouse brain. In primary neurons fr om the hippocampi of mouse embryos the expression of mCAR was observed thro ughout the cells including those in growth cones on immunohistochemistry. I n order to determine whether or not mCAR is involved in cell adhesion, aggr egation assays were carried out. C6 cells transfected with mCAR cDNA aggreg ated homophilically, which was inhibited by specific antibodies against the extracellular domain of mCAR. In addition to its action as a virus recepto r, mCAR may function naturally as an adhesion molecule involved in neuro-ne twork formation in the developing nervous system. (C) 2000 Elsevier Science BN. All rights reserved.