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Regulated axonal transport of APP and alcadein by kinesin‐1 (783.1)
Author(s) -
Suzuki Toshiharu,
Chiba Kyoko,
Okumura Yuka,
Shiraki Yuzuha,
Sobu Yuriko,
Kinjo Masataka,
Hata Saori,
Taru Hidenori
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.783.1
Subject(s) - kinesin , microbiology and biotechnology , gene isoform , chemistry , amyloid precursor protein , motor protein , mutant , biophysics , biology , biochemistry , microtubule , gene , alzheimer's disease , medicine , disease , pathology
Alzheimer’s β‐amyloid precursor protein (APP) and Alcadein (Alc) are cargo of kinesin‐1. APP associates to kinesin‐1 by JIP1b mediation, while Alc directly binds to kinesin‐1. APP is subject to axonal transport faster than Alc in independent cargos, even if both APP and Alc are transported kinesin‐1 in axon. To understand molecular mechanisms how both cargos are transported in different velocities, we revealed molecular interactions biochemically among APP, JIP1b and kinesin light chain (KLC), and between Alc and KLC. Methods: Detailed interaction between Alc and KLC, and JIP1b and KLC were analyzed biochemically by co‐immunoprecipitaion and GST pull‐down assays. We generated many deletion mutants for Alcα (one of Alcadein family) and JIP1b (JIP1 family which can bind APP strongly), and analyzed the interaction with KLC1 (neuron‐specific isoform of KLC) mutants. Function was investigated with analysis of APP‐GFP and Alcα‐GFP transport in neural axon with TRIF microscopy. Results and Discussion: Direct binding between Alcα and KLC shows a simple but strong affinity, while JIP1b‐mediated interaction between APP and KLC is more complex. The mediation of JIP1b may regulate fast velocity of anterograde cargo transport by kinesin‐1. Grant Funding Source : Supported by Grants‐in‐Aid for Scientific Research from JSPS, Japan.