Laryngeal dystonia in a patient with bilateral anterior cerebral artery infarction during treatment of delirium with haloperidol

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• 作者：Aysegul Sari ; Ozlem Taskapilioglu ; Cengiz Akkaya* ; Sevda Erer ; Ibrahim Bora
• 关键词：Dopamine transporter ; Calpain ; Receptor of activated protein kinase C ; RACK1
• 刊名：Progress in Neuro-Psychopharmacology and Biological Psychiatry
• 出版年：2008
• 出版时间：1 July 2008
• 年：2008
• 卷：32
• 期：5
• 页码：1347-1348
• 全文大小：119 K

文摘

It has been shown recently that the N-terminal domain of the dopamine transporter (DAT) plays a role in several transporter functions. Here we provide evidence for a possible cellular mechanism of how the N-terminus of dopamine transporter might be removed in vivo. We isolated a recombinant N-terminal protein region of human dopamine transporter and cleaved it with calpain protease. Peptide fragment analysis revealed the existence of two calpain cleavage sites at positions Thr43/Ser44 and Leu71/Ser72 of the DATN-terminus. We show that calpain activation in rat striatal synaptosomes leads to a rapid decrease of dopamine transporter N-terminal epitopes corresponding to the protein sequences removed by a calpain cleavage at Thr43/Ser44 and that the process is totally blocked by a calpain inhibitor. Calpain truncation of the DATN-terminus abolishes its interaction with the receptor of activated protein kinase C, RACK1 and removes protein sequences previously implicated in amphetamine-induced dopamine release, PKC-dependent endocytosis and the interaction of DAT with the dopamine D2 receptor. The above suggests that cleavage of DAT by calpain may significantly modify dopamine homeostasis under pathological or physiological conditions.