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 language | English (US) |
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Pages (from-to) | 834-848 |
Number of pages | 15 |
Journal | Traffic |
Volume | 13 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2012 |
Externally published | Yes |
Keywords
- Alcadein
- Calsyntenin
- JIP1
- KLC
- Kinesin-1
- Tetratricopeptide repeat
ASJC Scopus subject areas
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology