ARL13B regulates Sonic hedgehog signaling from outside primary cilia.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32129762.
- Also identified by DOI 10.7554/eLife.50434 and PMC identifier 7075693.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
ARL13B is a regulatory GTPase highly enriched in cilia. Complete loss of <i>Arl13b</i> disrupts cilia architecture, protein trafficking and Sonic hedgehog signaling. To determine whether ARL13B is required within cilia, we knocked in a cilia-excluded variant of ARL13B (V358A) and showed it retains all known biochemical function. We found that ARL13B<sup>V358A</sup> protein was expressed but could not be detected in cilia, even when retrograde ciliary transport was blocked. We showed <i>Arl13b<sup>V358A/V358A</sup></i> mice are viable and fertile with normal Shh signal transduction. However, in contrast to wild type cilia, <i>Arl13b<sup>V358A/V358A</sup></i> cells displayed short cilia and lacked ciliary ARL3 and INPP5E. These data indicate that ARL13B's role within cilia can be uncoupled from its function outside of cilia. Furthermore, these data imply that the cilia defects upon complete absence of ARL13B do not underlie the alterations in Shh transduction, which is unexpected given the requirement of cilia for Shh transduction.
Medical subject headings
- ADP-Ribosylation Factors
- Cilia
- Hedgehog Proteins
- Signal Transduction