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생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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The heterotrimeric kinesin-2 family member KIF3A directly binds to disabled-1 (Dab1)

  • Myoung Hun Kim (Department of Anesthesia and Pain Medicine, Busan Paik Hospital, Inje University) ;
  • Young Joo Jeong (Department of Biochemistry, College of Medicine, Inje University) ;
  • Sang-Hwa Urm (Department of Preventive Medicine, College of Medicine, Inje University) ;
  • Dae-Hyun Seog (Department of Biochemistry, College of Medicine, Inje University)
  • 투고 : 2024.02.15
  • 심사 : 2024.03.17
  • 발행 : 2024.10.31
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초록

The heterotrimeric molecular motor kinesin-2 is involved in the microtubule-dependent transport of intracellular cargo. It consists of two distinct motor subunits (KIF3A, and KIF3B) and a non-motor subunit, kinesin-associated protein 3 (KAP3). The cargo-binding domain (CBD) at the carboxyl (C)-terminus of KIF3s plays an important role in the interaction with several different binding proteins. To identify the binding proteins for heterotrimeric kinesin-2, we performed a yeast two-hybrid screen and found a new interaction with Disables-1 (Dab1), the intracellular adaptor protein of reelin receptors. Dab1 bound to the CBD of KIF3A, but did not interact with the C-terminal domain of KIF3B, KIF5B, KIF17 or KAP3. The phosphotyrosine binding (PTB) domain-containing region of Dab1 is essential for the interaction with KIF3A. KIF3A interacted with GST-Dab1, and GST-CaMKIIα , but did not interact with GST-apolipoprotein E receptor 2 (ApoER2)-C or with GST alone. When co-expressed in HEK-293T cells, Dab1 co-precipitated with KIF3A, but not with KIF5B. Dab1 and KIF3A were co-localized in cultured cells. We also identified deduced cell surface expression of ApoER2 in KIF3A dominant-negative cells. These results suggest that the KIF3A plays a role in the intracellular trafficking of ApoER2 to the cell surface.

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과제정보

We thank Dr. K. Kaibuchi (Nagoya University) for providing pcDNA-KIF3A, and Dr. S. Hisanada (Tokyo Metropolitan University) for providing pcDNA-Dab1. This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) by the Ministry of Education, Science and Technology under Grant (No. NRF-2019R1F1A1040903, and NRF-2022R1F1A1064272).

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