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Unveiling the Role of DJ-1 Protein in Vesicular Storage and Release of Catecholamine with Nano/Micro-Tip Electrodes
Authors:Qingwei Yue  Prof Xianchan Li  Dr Fei Wu  Wenliang Ji  Yue Zhang  Prof Ping Yu  Prof Meining Zhang  Dr Wenjie Ma  Prof Ming Wang  Prof Lanqun Mao
Institution:1. Beijing National Laboratory for Molecular Science, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences (CAS), CAS Research/Education Center for Excellence in Molecule Science, Beijing, 100190 China

University of Chinese Academy of Sciences, Beijing, 100049 China

These authors contributed equally to this work.;2. Beijing National Laboratory for Molecular Science, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences (CAS), CAS Research/Education Center for Excellence in Molecule Science, Beijing, 100190 China

These authors contributed equally to this work.;3. Beijing National Laboratory for Molecular Science, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences (CAS), CAS Research/Education Center for Excellence in Molecule Science, Beijing, 100190 China

University of Chinese Academy of Sciences, Beijing, 100049 China;4. Department of Chemistry, Renmin University of China, Beijing, 100872 China;5. Beijing National Laboratory for Molecular Science, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences (CAS), CAS Research/Education Center for Excellence in Molecule Science, Beijing, 100190 China

Abstract:DJ-1 protein deficiency caused by PARK7 gene mutation has been suggested to closely relate to Parkinson's disease (PD), mainly through the attenuation D2 dopamine receptor activity in mice; however, whether or how it affects the vesicular storage and exocytosis of neurochemicals remains unclear. By using electrochemical methods at a single vesicle/cell level with nano/micro-tip electrodes, we for the first time find that DJ-1 protein deficiency caused by PARK7 gene knockout (KO) in mice has little effect on vesicular catecholamine content but significantly prolongs the exocytotic events, especially the closing time of exocytotic fusion pores. Further studies suggest the inhibition of α-synuclein aggregation by DJ-1 protein might be one way that DJ-1 protein acts on neurotransmission. This finding offers the first direct link between DJ-1 protein deficiency and vesicular chemical storage and release of chemicals, providing a new chemical insight into the pathology of PD caused by PARK7 gene mutation.
Keywords:DJ-1 protein  electroanalysis  exocytosis  Parkinson's disease  protein–protein interactions
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