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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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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)
  • Received : 2024.02.15
  • Accepted : 2024.03.17
  • Published : 2024.10.31
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Abstract

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.

Keywords

Acknowledgement

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).

References

  1. Hirokawa N (1988) Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279, 519-526
  2. Hirokawa N (2000) Stirring up development with the heterotrimeric kinesin KIF3. Traffic 1, 29-34
  3. Seog DH, Lee DH and Lee SK (2004) Molecular motor proteins of the kinesin superfamily proteins (KIFs): structure, cargo and disease. J Korean Med Sci 19, 1-7
  4. Hirokawa N, Niwa S and Tanaka Y (2010) Molecular motors in neurons: transport mechanisms and roles in brain function, development, and disease. Neuron 68, 610-638
  5. Scholey JM (2013) Kinesin-2: a family of heterotrimeric and homodimeric motors with diverse intracellular transport functions. Annu Rev Cell Dev Biol 29, 443-469
  6. Yamazaki H, Nakata T, Okada Y and Hirokawa N (1996) Cloning and characterization of KAP3: a novel kinesin superfamily-associated protein of KIF3A/3B. Proc Natl Acad Sci U S A 93, 8443-8448
  7. Takeda S, Yamazaki H, Seog DH et al (2000) Kinesin superfamily protein 3 (KIF3) motor transports fodrin-associating vesicles important for neurite building. J Cell Biol 148, 1255-1265
  8. Ichinose S, Ogawa T and Hirokawa N (2015) Mechanism of activity-dependent cargo loading via the phosphorylation of KIF3A by PKA and CaMKIIα. Neuron 87, 1022-1035
  9. Kovacs JJ, Whalen EJ, Liu R et al (2008) Beta-arrestin-mediated localization of smoothened to the primary cilium. Science 320, 1777-1781
  10. Kodani A, Salome Sirerol-Piquer M, Seol A et al (2013) Kif3a interacts with Dynactin subunit p150 Glued to organize centriole subdistal appendages. EMBO J 32, 597-607
  11. Fuchigami T, Sato Y, Tomita Y et al (2013) Dab1-mediated colocalization of multi-adaptor protein CIN85 with Reelin receptors, ApoER2 and VLDLR, in neurons. Genes Cells 18, 410-424
  12. Margolis B, Borg JP, Straight S and Meyer D (1999) The function of PTB domain proteins. Kidney Int 56, 1230-1237
  13. Yoshihara S, Jiang X, Morikawa M et al (2021) Betaine ameliorates schizophrenic traits by functionally compensating for KIF3-based CRMP2 transport. Cell Rep 35, 108971
  14. Lane-Donovan C and Herz J (2017) ApoE, ApoE receptors, and the synapse in Alzheimer's disease. Trends Endocrinol Metab 28, 273-284
  15. Honda T and Nakajima K (2016) Proper level of cytosolic Disabled-1, which is regulated by dual nuclear translocation pathways, is important for cortical neuronal migration. Cereb Cortex 26, 3219-3236
  16. Hoe HS, Tran TS, Matsuoka Y, Howell BW and Rebeck GW (2006) DAB1 and Reelin effects on amyloid precursor protein and ApoE receptor 2 trafficking and processing. J Biol Chem 281, 35176-35185
  17. Ma SL, Ng HK, Baum L et al (2002) Low-density lipoprotein receptor-related protein 8 (apolipoprotein E receptor 2) gene polymorphisms in Alzheimer's disease. Neurosci Lett 332, 216-218
  18. Wang W, Moerman-Herzog AM, Slaton A and Barger SW (2017) Presenilin 1 mutations influence processing and trafficking of the ApoE receptor ApoER2. Neurobiol Aging 49, 145-153
  19. Sun F, Zhu C, Dixit R and Cavalli V (2011) Sunday Driver/JIP3 binds kinesin heavy chain directly and enhances its motility. EMBO J 30, 3416-3429
  20. Verhey KJ, Meyer D, Deehan R et al (2001) Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules. J Cell Biol 152, 959-970
  21. Nakajima K, Yin X, Takei Y et al (2012) Molecular motor KIF5A is essential for GABA(A) receptor transport, and KIF5A deletion causes epilepsy. Neuron 76, 945-961
  22. Nabb AT, Frank M and Bentley M (2020) Smart motors and cargo steering drive kinesin-mediated selective transport. Mol Cell Neurosci 103, 103464
  23. Nishimura T, Kato K, Yamaguchi T et al (2004) Role of the PAR-3-KIF3 complex in the establishment of neuronal polarity. Nat Cell Biol 6, 328-334
  24. Jang WH, Jeong YJ, Choi SH et al (2014) Dynamin-1-like protein (Dnm1L) interaction with kinesin light chain 1 (KLC1) through the tetratricopeptide repeat (TPR) domains. Biosci Biotechnol Biochem 78, 2069-2072