Mechanism and physiological role for generation of the carboxyl terminal fragment of the P/Q-type calcium channel

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Generation of Cav2. 1 carboxyl terminal tail(Cav2. 1CT) is thought to be causally related to spinocerebellar ataxia type 6, a hereditary neurological disease. Cav2. 1CT is generated by cleavage of the full-length Cav2. 1 protein. But the exact mechanism underlying the generation of Cav2. 1CT and the function of this CT fragment remain to be clarified. In the present study, I have tried to clarify the mechanism to generate the Cav2. 1CT from full-length Cav2. 1 protein. Also, I have studied the functional role of the Cav2. 1CT in some in vitro systems. As a result, the following molecules are candidates for the protease responsible for the Cav2. 1CT generation : caspase 6, cathepsin L, and calpain small subunit 1, but further studies are necessary to conclude this. Cav2. 1CT was found to be toxic to cells and it is possible that Cav2. 1CT possess transcription repressing activity