• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner



Axonal Transport and Cytoskeleton

開催日 2014/9/13
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Alcadein drives kinesin-1 and undergoes constitutive limited proteolysis to maintain proper distribution of kinesin-1

  • P3-012
  • 山本 融 / Tohru Yamamoto:1 豊島 哲彦 / Tetsuhiko Toyoshima:1 丸田 千明 / Chiaki Maruta:2 荒関 雅彦 / Masahiko Araseki:2 鈴木 利治 / Toshiharu Suzuki:2 
  • 1:香川大・医・分子神経 / Dept Mol. Neurobiol., Fac Med., Kagawa Univ, Kagawa, Japan 2:北大院・薬・神経科学 / Lab Neurosci., Fac Pharm. Sci., Hokkaido Univ, Hokkaido, Japan 

Alcadeinα (Alcα; also known as Calsyntenin-1) is an evolutionary conserved single pass type I transmembrane protein primarily expressed by neurons. Alcα interacts with a light chain subunit of kinesin-1 (KLC) through a ~10 amino acids structure named WD-motif after its indispensable amino acid residues for its binding to KLC. WD-motif is located in its C-terminal cytoplasmic domain, through which Alcα activates kinesin-1's association with Alcα-containing vesicles. We characterized the function of the WD motif structure on Kinesin-1 activation by creating a novel artificial membrane protein. The artificial proteins were efficiently incorporated in various vesicles and transported with various velocities; however, the same proteins containing WD-motif structure were transported by Kinesin-1 with a defined velocity. We further showed evidences indicating that WD-motif structure is sufficient for initiating activation of Kinesin-1. These findings lead a question: Given that WD motif structure is sufficient for activating Kinesin-1, Kinesin-1 would be constitutively activated around a cell periphery where Alcα proteins should be transported to lead aberrant retention of Kinesin-1 which might cause an inadequate morphological alteration on neurons? Since such abnormalities were never observed, we further investigated the reason why those never happened in neurons. We found that Alcα proteins were so constitutively and efficiently cleaved that the full-length proteins were never observed on plasma membranes. We further showed evidences indicating that Alcα proteins were efficiently cleaved en rout to and/or upon reaching the cell surface, and uncleavable mutant Alcα aberrantly retained Kinesin-1 around the cell periphery. These findings collectively suggested that Alcα can dictate initiation of Kinesin-1 activation without particular cooperation of additional factors but should be shattered soon after accomplishing its duty, partly for maintaining proper intracellular distribution of Kinesin-1. Our findings may exemplify a homeostatic regulation of axonal transport.

Copyright © Neuroscience2014. All Right Reserved.