The heterotrimeric kinesin-2 family member KIF3A directly binds to disabled-1 (Dab1)
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The heterotrimeric molecular motor kinesin-2 is involved inthe microtubule-dependent transport of intracellular cargo. Itconsists of two distinct motor subunits (KIF3A, and KIF3B) anda non-motor subunit, kinesin-associated protein 3 (KAP3). Thecargo-binding domain (CBD) at the carboxyl (C)-terminus ofKIF3s plays an important role in the interaction with severaldifferent binding proteins. To identify the binding proteins forheterotrimeric kinesin-2, we performed a yeast two-hybrid screenand found a new interaction with Disables-1 (Dab1), the intracellularadaptor protein of reelin receptors. Dab1 bound tothe CBD of KIF3A, but did not interact with the C-terminal domainof KIF3B, KIF5B, KIF17 or KAP3. The phosphotyrosine binding(PTB) domain-containing region of Dab1 is essential for theinteraction with KIF3A. KIF3A interacted with GST-Dab1, andGST-CaMKII, but did not interact with GST-apolipoprotein Ereceptor 2 (ApoER2)-C or with GST alone. When co-expressedin HEK-293T cells, Dab1 co-precipitated with KIF3A, but notwith KIF5B. Dab1 and KIF3A were co-localized in cultured cells. We also identified deduced cell surface expression of ApoER2in KIF3A dominant-negative cells. These results suggest that theKIF3A plays a role in the intracellular trafficking of ApoER2 tothe cell surface.
Abstract
The heterotrimeric molecular motor kinesin-2 is involved inthe microtubule-dependent transport of intracellular cargo. Itconsists of two distinct motor subunits (KIF3A, and KIF3B) anda non-motor subunit, kinesin-associated protein 3 (KAP3). Thecargo-binding domain (CBD) at the carboxyl (C)-terminus ofKIF3s plays an important role in the interaction with severaldifferent binding proteins. To identify the binding proteins forheterotrimeric kinesin-2, we performed a yeast two-hybrid screenand found a new interaction with Disables-1 (Dab1), the intracellularadaptor protein of reelin receptors. Dab1 bound tothe CBD of KIF3A, but did not interact with the C-terminal domainof KIF3B, KIF5B, KIF17 or KAP3. The phosphotyrosine binding(PTB) domain-containing region of Dab1 is essential for theinteraction with KIF3A. KIF3A interacted with GST-Dab1, andGST-CaMKII, but did not interact with GST-apolipoprotein Ereceptor 2 (ApoER2)-C or with GST alone. When co-expressedin HEK-293T cells, Dab1 co-precipitated with KIF3A, but notwith KIF5B. Dab1 and KIF3A were co-localized in cultured cells. We also identified deduced cell surface expression of ApoER2in KIF3A dominant-negative cells. These results suggest that theKIF3A plays a role in the intracellular trafficking of ApoER2 tothe cell surface.
참고문헌 (24)
- Hirokawa N, "Kinesin and dynein superfamily proteins and the mechanism of organelle transport", Science, 279, pp.519~526 (1988)
- Hirokawa N, "Stirring up development with the heterotrimeric kinesin KIF3", Traffic, 1, pp.29~34 (2000)
- Seog DH, "Molecular motor proteins of the kinesin superfamily proteins(KIFs) : structure, cargo and disease", J Korean Med Sci, 19, pp.1~7 (2004)
- Hirokawa N, "Molecular motors in neurons : transport mechanisms and roles in brain function, development, and disease", Neuron, 68, pp.610~638 (2010)
- Scholey JM, "Kinesin-2 : a family of heterotrimeric and homodimeric motors with diverse intracellular transport functions", Annu Rev Cell Dev Biol, 29, pp.443~469 (2013)
- Yamazaki H, "Cloning and characterization of KAP3 : a novel kinesin superfamily-associated protein of KIF3A", 3B, 1996, pp.93, 8443~8448
- Takeda S, "Kinesin superfamily protein 3(KIF3)motor transports fodrin-associating vesicles important for neurite building", J Cell Biol, 148, pp.1255~1265 (2000)
- Ichinose S, "Mechanism of activity-dependent cargo loading via the phosphorylation of KIF3A by PKA and CaMKII", Neuron, 87, pp.1022~1035 (2015)
- Kovacs JJ, "Beta-arrestin-mediated localization of smoothened to the primary cilium", Science, 320, pp.1777~1781 (2008)
- Kodani A, "Kif3a interacts with Dynactin subunit p150 Glued to organize centriole subdistal appendages", EMBO J, 32, pp.597~607 (2013)
- Fuchigami T, "Dab1-mediated colocalization of multi-adaptor protein CIN85 with Reelin receptors, ApoER2 and VLDLR, in neurons", Genes Cells, 18, pp.410~424 (2013)
- Margolis B, "The function of PTB domain proteins", Kidney Int, 56, pp.1230~1237 (1999)
- Yoshihara S, "Betaine ameliorates schizophrenic traits by functionally compensating for KIF3-based CRMP2 transport", Cell Rep, 35, pp.108971~ (2021)
- Lane-Donovan C, "ApoE, ApoE receptors, and the synapse in Alzheimer’s disease", Trends Endocrinol Metab, 28, pp.273~284 (2017)
- Honda T, "Proper level of cytosolic Disabled-1, which is regulated by dual nuclear translocation pathways, is important for cortical neuronal migration", Cereb Cortex, 26, pp.3219~3236 (2016)
- Hoe HS, "DAB1 and Reelin effects on amyloid precursor protein and ApoE receptor 2 trafficking and processing", J Biol Chem, 281, pp.35176~35185 (2006)
- Ma SL, "Low-density lipoprotein receptor-related protein 8(apolipoprotein E receptor 2)gene polymorphisms in Alzheimer’s disease", Neurosci Lett, 332, pp.216~218 (2002)
- Wang W, "Presenilin 1 mutations influence processing and trafficking of the ApoE receptor ApoER2", Neurobiol Aging, 49, pp.145~153 (2017)
- Sun F, "Sunday Driver", JIP3 binds kinesin heavy chain directly and enhances its motility, 2011, pp.30, 3416~3429
- Verhey KJ, "Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules", J Cell Biol, 152, pp.959~970 (2001)
- Nakajima K, "Molecular motor KIF5A is essential for GABA(A)receptor transport, and KIF5A deletion causes epilepsy", Neuron, 76, pp.945~961 (2012)
- Nabb AT, "Smart motors and cargo steering drive kinesin-mediated selective transport", Mol Cell Neurosci, 103, pp.103464~ (2020)
- Nishimura T, "Role of the PAR-3-KIF3 complex in the establishment of neuronal polarity", Nat Cell Biol, 6, pp.328~334 (2004)
- Jang WH, "Dynamin-1-like protein(Dnm1L)interaction with kinesin light chain 1(KLC1)through the tetratricopeptide repeat(TPR)domains", Biosci Biotechnol Biochem, 78, pp.2069~2072 (2014)