The novel cargo Alcadein induces vesicle association of kinesin-1 motor components and activates axonal transport

Yoichi Araki, Takanori Kawano, Hidenori Taru, Yuhki Saito, Sachiyo Wada, Kanako Miyamoto, Hisako Kobayashi, Hiroyuki O. Ishikawa, Yu Ohsugi, Tohru Yamamoto, Kenji Matsuno, Masataka Kinjo, Toshiharu Suzuki

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

Alcadeinα (Alcα) is an evolutionarily conserved type I membrane protein expressed in neurons. We show here that Alcα strongly associates with kinesin light chain (KD≈4-8 × 10-9 M) through a novel tryptophan- and aspartic acid-containing sequence. Alcα can induce kinesin-1 association with vesicles and functions as a novel cargo in axonal anterograde transport. JNK-interacting protein 1 (JIP1), an adaptor protein for kinesin-1, perturbs the transport of Alcα, and the kinesin-1 motor complex dissociates from Alcα-containing vesicles in a JIP1 concentration-dependent manner. Alcα-containing vesicles were transported with a velocity different from that of amyloid β-protein precursor (APP)-containing vesicles, which are transported by the same kinesin-1 motor. Alcα- and APP-containing vesicles comprised mostly separate populations in axons in vivo. Interactions of Alcα with kinesin-1 blocked transport of APP-containing vesicles and increased β-amyloid generation. Inappropriate interactions of Alc- and APP-containing vesicles with kinesin-1 may promote aberrant APP metabolism in Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)1475-1486
Number of pages12
JournalEMBO Journal
Volume26
Issue number6
DOIs
StatePublished - Mar 21 2007
Externally publishedYes

Keywords

  • APP
  • Alcadein
  • Alzheimer's disease
  • Axonal transport
  • Kinesin

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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