Coxsackie and adenovirus receptor (CAR): functions of a novel adhesion molecule

柯萨奇和腺病毒受体（CAR）是免疫球蛋白粘附分子超家族的新成员。顾名思义，它首先被鉴定为5型腺病毒的高亲和力受体，5型腺病毒是最常用的用于基因转移的腺病毒载体。我的实验室对CAR的兴趣源于我们常规使用腺病毒（Ad）载体将基因转移到肌肉、神经系统和肿瘤细胞。因此，我们对确定CAR的表达模式和调节其表达的方法以及检查其在这些组织中的功能很感兴趣。

The Coxsackie and adenovirus receptor (CAR) is a novel member of the immunoglobulin superfamily of adhesion molecules. As its name implies, it was first identified as the high affinity receptor for adenovirus type 5, the most commonly used adenoviral vector for gene transfer. My laboratory's interest in CAR stems from our routine use adenovirus (Ad) vectors for gene transfer to muscle, nervous system and tumour cells. Thus, we have been interested in determining the expression pattern of CAR and means of modulating its expression, as well as examining its function in these tissues. CAR expression is regulated developmentally and in a tissue-specific manner. Highest levels of CAR expression are observed in prenatal and neonatal tissues. This pattern of expression suggests CAR could play a role in the growth, migration or differentiation of embryonic or neonatal tissues. Such a role for CAR is further supported by the observation of loss of CAR expression in several types of cancer. Our long term objective is to understand how an adhesion molecule such as CAR transmits extracellular cues into intracellular signals. We have concentrated on two biological systems, tumour cells and neurons. In both cell types, CAR plays crucial roles in cell migration. In tumour cells, CAR expression leads to inhibition of migration and invasion while in neurons, CAR expression promotes process extension (neurite outgrowth). We have shown CAR can undergo metalloprotease-mediated shedding of its extracellular domain, followed by cleavage through the gamma-secretase complex to produce an intracellular cytoplasmic fragment, thus generating potentially important signalling molecules. CAR expression is highest in the developing nervous system, making primary neuronal cultures and mouse embryonic nervous system development the ideal experimental models to study CAR function. Our specific objectives are to:1) determine the functional relevance of the proteolytic processing of CAR; 2) determine whether CAR's intracellular cytoplasmic domain plays a signaling role; 3) study the function of CAR in the developing nervous system.