KMID : 0624620210540070380
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BMB Reports 2021 Volume.54 No. 7 p.380 ~ p.385
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Kinesin-1-dependent transport of the ¥âPIX/GIT complex in neuronal cells
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Shin Eun-Young
Lee Chan-Soo Kim Han-Byeol Park Jin-Hee Oh Kwang-Seok Lee Gun-Wu Cho Eun-Yul Kim Hyong-Kyu Kim Eung-Gook
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Abstract
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Proper targeting of the ¥âPAK-interacting exchange factor (¥âPIX)/G protein-coupled receptor kinase-interacting target protein (GIT) complex into distinct cellular compartments is essential for its diverse functions including neurite extension and synaptogenesis. However, the mechanism for translocation of this complex is still unknown. In the present study, we reported that the conventional kinesin, called kinesin-1, can transport the ¥âPIX/GIT complex. Additionally, ¥âPIX bind to KIF5A, a neuronal isoform of kinesin-1 heavy chain, but not KIF1 and KIF3. Mapping analysis revealed that the tail of KIF5s and LZ domain of ¥âPIX were the respective binding domains. Silencing KIF5A or the expression of a variety of mutant forms of KIF5A inhibited ¥âPIX targeting the neurite tips in PC12 cells. Furthermore, truncated mutants of ¥âPIX without LZ domain did not interact with KIF5A, and were unable to target the neurite tips in PC12 cells. These results defined kinesin-1 as a motor protein of ¥âPIX, and may provide new insights into ¥âPIX/GIT complex-dependent neuronal pathophysiology.
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KEYWORD
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¥âPAK-interacting exchange factor (¥âPIX), G proteincoupled receptor kinase-interacting target protein (GIT), Kinesin-1, Neuron, Transport
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