A Small Peptide Sequence is Sufficient for Initiating Kinesin-1 Activation Through Part of TPR Region of KLC1

Takanori Kawano, Masahiko Araseki, Yoichi Araki, Masataka Kinjo, Tohru Yamamoto, Toshiharu Suzuki

Research output: Contribution to journalArticlepeer-review

Abstract

Kinesin-1 anterogradely transports vesicles containing cargo proteins when a protein-protein interaction activates it from an inhibited state. The C-terminal cytoplasmic region of kinesin-1 cargo protein Alcadeinα (Alcα) interacts with the KLC1 subunit's tetratricopeptide repeat (TPR) region, activating kinesin-1's association with vesicles and anterograde transport. We found that either of two 10-amino-acid WD motifs in Alcα cytoplasmic region was necessary and sufficient to initiate this activation. An artificial transmembrane protein containing either WD motif induced kinesin-1's vesicular association and anterograde transport in a KLC-dependent manner, even in the normally inhibiting presence of excess KLC1, thus allowing us to analyze the KLC1 TPR-WD functional interaction in detail in vivo. A part of TPR region was dispensable for the WD motifs' activation of kinesin-1 and transport, indicating that only part of the TPR structure is required for this function in vivo. For a different kinesin-1 cargo protein, JIP1, an 11-amino-acid C-terminal region was sufficient to recruit KLC1 to vesicles, but did not activate transport. These observations suggest that structurally different TPR-interacting peptides may have different effects on kinesin-1. This mechanism may partly explain how kinesin-1 can organize the transport of a wide variety of cargo molecules.

Original languageEnglish (US)
Pages (from-to)834-848
Number of pages15
JournalTraffic
Volume13
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Alcadein
  • Calsyntenin
  • JIP1
  • KLC
  • Kinesin-1
  • Tetratricopeptide repeat

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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