title: A small peptide sequence is sufficient for initiating kinesin-1 activation through part of TPR region of KLC1.
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.
authors.affiliation: Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Kawano
authors.forename: Masahiko
authors.initials: M
authors.lastname: Araseki
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Araki
authors.forename: Masataka
authors.initials: M
authors.lastname: Kinjo
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry*; D008954:Models, Biological; D010455:Peptides / Q000737:chemistry*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: C000715688:KLC1 protein, human; C000715690:Klc1 protein, rat; C000715695:Kns2 protein, mouse; D008869:Microtubule-Associated Proteins; D010455:Peptides; D049452:Green Fluorescent Proteins; D016547:Kinesins