Primary cilia function as critical signaling hubs whose absence leads to severe disorders collectively known as ciliopathies; our knowledge of ciliogenesis remains limited. We show that Smo induces ciliogenesis through two distinct yet essential noncanonical Hh pathways in several cell types, including neurons. Surprisingly, ligand activation of Smo induces autophagy via an LKB1-AMPK axis to remove the satellite pool of OFD1. This is required, but not sufficient, for ciliogenesis. Additionally, Smo activates the Gαi-LGN-NuMA-dynein axis, causing accumulation of a portion of OFD1 at centrioles in early ciliogenesis. Both pathways are critical for redistribution of BBS4 from satellites to centrioles, which is also mediated by OFD1 centriolar translocation. Notably, different Smo agonists, which activate Smo distinctly, activate one or the other of these pathways; only in combination they recapitulate the activity of Hh ligand. These studies provide new insight into physiological stimuli (Hh) that activate autophagy and promote ciliogenesis and introduce a novel role for the Gαi-LGN-NuMA-dynein complex in this process.
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4 January 2021
Article|
December 01 2020
A non-canonical Hedgehog pathway initiates ciliogenesis and autophagy
Tara Akhshi
,
Tara Akhshi
1
Cell Biology Program, Hospital for Sick Children, Toronto, Canada
2
Department of Biochemistry, University of Toronto, Toronto, Canada
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William S. Trimble
1
Cell Biology Program, Hospital for Sick Children, Toronto, Canada
2
Department of Biochemistry, University of Toronto, Toronto, Canada
Correspondence to William S. Trimble: wtrimble@sickkids.ca
Search for other works by this author on:
Tara Akhshi
1
Cell Biology Program, Hospital for Sick Children, Toronto, Canada
2
Department of Biochemistry, University of Toronto, Toronto, Canada
William S. Trimble
1
Cell Biology Program, Hospital for Sick Children, Toronto, Canada
2
Department of Biochemistry, University of Toronto, Toronto, Canada
Correspondence to William S. Trimble: wtrimble@sickkids.ca
Received:
April 21 2020
Revision Received:
August 19 2020
Accepted:
October 14 2020
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding:
Hospital for Sick Children
(NO AWARD)
© 2020 Akhshi and Trimble
2020
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2021) 220 (1): e202004179.
Article history
Received:
April 21 2020
Revision Received:
August 19 2020
Accepted:
October 14 2020
Citation
Tara Akhshi, William S. Trimble; A non-canonical Hedgehog pathway initiates ciliogenesis and autophagy. J Cell Biol 4 January 2021; 220 (1): e202004179. doi: https://doi.org/10.1083/jcb.202004179
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