Kinesin-1-dependent transport of the βPIX/GIT complex in neuronal cells

• Published in: BMB reports 2021-07, Vol.54 (7), p.380-385
• Main Authors: Shin, Eun-Young, Lee, Chan-Soo, Kim, Han-Byeol, Park, Jin-Hee, Oh, Kwangseok, Lee, Gun-Wu, Cho, Eun-Yul, Kim, Hyong Kyu, Kim, Eung-Gook
• Format: Article
• Language: Korean
• Subjects: G proteincoupled receptor kinase-interacting target protein; GIT; Kinesin-1; Neuron; Transport; βPAK-interacting exchange factor; βPIX
• ISSN: 1976-6696; 1976-670X

Proper targeting of the βPAK-interacting exchange factor (βPIX)/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 βPIX/GIT complex. Additionally, βPIX 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 βPIX were the respective binding domains. Silencing KIF5A or the expression of a variety of mutant forms of KIF5A inhibited βPIX targeting the neurite tips in PC12 cells. Furthermore, truncated mutants of βPIX 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 βPIX, and may provide new insights into βPIX/GIT complex-dependent neuronal pathophysiology. [BMB Reports 2021; 54(7): 380-385]