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Transport of APP and Alcadein by kinesin‐1
Author(s) -
Suzuki Toshiharu,
Araki Yoichi,
Kawano Takanori,
Akiyama Mayu,
Arakawa Takahiro,
Urano Satomi,
Kawai Tomoko,
Matsushima Takahide,
Nakaya Tadashi,
Yamamoto Tohru,
Kinjyo Masataka
Publication year - 2007
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.21.6.lb35-c
Subject(s) - kinesin , axoplasmic transport , amyloid precursor protein , microbiology and biotechnology , vesicular transport protein , immunoprecipitation , transport protein , vesicular transport proteins , chemistry , biophysics , biology , alzheimer's disease , biochemistry , vesicle , endosome , microtubule , membrane , gene , medicine , pathology , disease , vacuolar protein sorting , intracellular
Purpose: Amyloid β‐protein precursor (APP) and Alcadein (Alc) are subjected to vesicular transport to nerve terminus. Disruption of vesicular transport system induces an amyloidogenic processing of APP. We analyzed players related to vesicular transport of APP and Alc. Methods: To identify proteins regulating vesicular transport of APP and Alc, yeast two‐hybrid screen, pull‐down assay, and coimmunoprecipitation studies were performed. To examine the axonal transport of APP and Alc, GFP‐APP and GFP‐Alc were expressed in neuronal cells, and observed using TIRF microscopy system. Results: APP associated with KLC through JIP1b bridging, while Alc directly associated to KLC with strong affinity. APP‐cargos and Alc‐cargos were subjected to anterograde transport independently with different velocity while both cargos were connected to the same kinesin‐1 motor. Excess amount of Alc‐cargos blocked transport of APP‐cargos and altered Aβ generation. Discussion: Defects of axonal tyransport system by inappropriate interactions of APP and Alc may be a primary cause of pathogenesis prior to Aβ generation in Alzheimer’s disease.