The Ciliary Protein Arl13b Functions Outside of the Primary Cilium in Shh-Mediated Axon Guidance.
Arl13b
Sonic Hedgehog
axon guidance
commissural neurons
primary cilia
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
10 12 2019
10 12 2019
Historique:
received:
31
05
2019
revised:
19
09
2019
accepted:
04
11
2019
entrez:
12
12
2019
pubmed:
12
12
2019
medline:
24
9
2020
Statut:
ppublish
Résumé
The small GTPase Arl13b is enriched in primary cilia and regulates Sonic hedgehog (Shh) signaling. During neural development, Shh controls patterning and proliferation through a canonical, transcription-dependent pathway that requires the primary cilium. Additionally, Shh controls axon guidance through a non-canonical, transcription-independent pathway whose connection to the primary cilium is unknown. Here we show that inactivation of Arl13b results in defective commissural axon guidance in vivo. In vitro, we demonstrate that Arl13b functions autonomously in neurons for their Shh-dependent guidance response. We detect Arl13b protein in axons and growth cones, far from its well-established ciliary enrichment. To test whether Arl13b plays a non-ciliary function, we used an engineered, cilia-localization-deficient Arl13b variant and found that it was sufficient to mediate Shh axon guidance in vitro and in vivo. Together, these results indicate that, in addition to its ciliary role in canonical Shh signaling, Arl13b plays a cilia-independent role in Shh-mediated axon guidance.
Identifiants
pubmed: 31825820
pii: S2211-1247(19)31486-X
doi: 10.1016/j.celrep.2019.11.015
pmc: PMC6927553
mid: NIHMS1546253
pii:
doi:
Substances chimiques
Arl13b protein, mouse
0
Hedgehog Proteins
0
ADP-Ribosylation Factors
EC 3.6.5.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3356-3366.e3Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM122568
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS090029
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY006360
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM122549
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM110663
Pays : United States
Organisme : NEI NIH HHS
ID : T32 EY007092
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS055077
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008605
Pays : United States
Organisme : NINDS NIH HHS
ID : T32 NS096050
Pays : United States
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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