Abstract
The Hedgehog (Hh) family of secreted proteins governs many key developmental processes by regulating Ci/Gli transcription factors at multiple levels including nuclear-cytoplasmic shuttling. Here, we investigate the mechanism underlying the regulation of Ci/Gli subcellular localization by identifying and characterizing a novel nuclear localization sequence (NLS) in the N-terminal conserved domain of Ci/Gli that matches the PY-NLS consensus. We demonstrate that the PY-NLS functions in parallel with a previously identified bipartite NLS to promote nuclear localization and activity of full-length Ci. We find that Transportin (Trn), the Drosophila homolog of Kapβ2, is responsible for PY-NLS-mediated nuclear localization of Ci. Furthermore, we show that the tumor suppressor and conserved Hh pathway component Suppressor of fused (Sufu) opposes Trn-mediated Ci nuclear import by masking its PY-NLS. Finally, we provide evidence that Gli proteins also contain a functional PY-NLS and that mammal Sufu uses a similar mechanism to regulate nuclear translocation of Gli. Our study not only provides a mechanistic insight into how Sufu regulates Hh signaling and the subcellular localization of Ci/Gli, but also reveals a role for Trn/Kapb2 in developmental regulation
Original language | English (US) |
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Pages (from-to) | 1092-1103 |
Number of pages | 12 |
Journal | Journal of cell science |
Volume | 127 |
Issue number | 5 |
DOIs | |
State | Published - Mar 2014 |
Keywords
- Ci
- Gli
- Hedgehog
- Py-nls
- Sufu
- Transportin
ASJC Scopus subject areas
- Cell Biology