期刊
JOURNAL OF CELL SCIENCE
卷 128, 期 5, 页码 1034-1050出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.162552
关键词
Hedgehog; GLI; KAP3; Kinesin-2; KIF3
类别
资金
- University of Michigan Center for Organogenesis
- American Heart Association scientist development grant [11SDG6380000]
- National Institutes of Health [R21 CA167122, R01 DC014428, R01 GM070862]
GLI transport to the primary cilium and nucleus is required for proper Hedgehog (HH) signaling; however, the mechanisms that mediate these trafficking events are poorly understood. Kinesin-2 motor proteins regulate ciliary transport of cargo, yet their role in GLI protein function remains unexplored. To examine a role for the heterotrimeric KIF3A-KIF3B-KAP3 kinesin-2 motor complex in regulating GLI activity, we performed a series of structure-function analyses using biochemical, cell signaling and in vivo approaches that define novel specific interactions between GLI proteins and two components of this complex, KAP3 and KIF3A. We find that all three mammalian GLI proteins interact with KAP3 and we map specific interaction sites in both proteins. Furthermore, we find that GLI proteins interact selectively with KIF3A, but not KIF3B, and that GLI interacts synergistically with KAP3 and KIF3A. Using a combination of cell signaling assays and chicken in ovo electroporation, we demonstrate that KAP3 interactions restrict GLI activator function but not GLI repressor function. These data suggest that GLI interactions with KIF3A-KIF3B-KAP3 complexes are essential for proper GLI transcriptional activity.
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