Schizophrenia-associated dysbindin modulates axonal mitochondrial movement in cooperation with p150 glued .

Autor: Suh BK; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea., Lee SA; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea., Park C; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.; Weill Institute of Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, USA., Suh Y; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea., Kim SJ; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea., Woo Y; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea., Nhung TTM; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea., Lee SB; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea., Mun DJ; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea., Goo BS; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea., Choi HS; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.; Department of Chemical Engineering, Pohang University of Science and Technology, Pohang, Republic of Korea., Kim SJ; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea., Park SK; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea. skpark@postech.ac.kr.
Jazyk: angličtina
Zdroj: Molecular brain [Mol Brain] 2021 Jan 18; Vol. 14 (1), pp. 14. Date of Electronic Publication: 2021 Jan 18.
DOI: 10.1186/s13041-020-00720-3
Abstrakt: Mitochondrial movement in neurons is finely regulated to meet the local demand for energy and calcium buffering. Elaborate transport machinery including motor complexes is required to deliver and localize mitochondria to appropriate positions. Defects in mitochondrial transport are associated with various neurological disorders without a detailed mechanistic information. In this study, we present evidence that dystrobrevin-binding protein 1 (dysbindin), a schizophrenia-associated factor, plays a critical role in axonal mitochondrial movement. We observed that mitochondrial movement was impaired in dysbindin knockout mouse neurons. Reduced mitochondrial motility caused by dysbindin deficiency decreased the density of mitochondria in the distal part of axons. Moreover, the transport and distribution of mitochondria were regulated by the association between dysbindin and p150 glued . Furthermore, altered mitochondrial distribution in axons led to disrupted calcium dynamics, showing abnormal calcium influx in presynaptic terminals. These data collectively suggest that dysbindin forms a functional complex with p150 glued that regulates axonal mitochondrial transport, thereby affecting presynaptic calcium homeostasis.
Databáze: MEDLINE
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