ARL13B regulates Sonic hedgehog signaling from outside primary cilia.

ELife
Eduardo D GiganteTamara Caspary

Abstract

ARL13B is a regulatory GTPase highly enriched in cilia. Complete loss of Arl13b 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 ARL13BV358A protein was expressed but could not be detected in cilia, even when retrograde ciliary transport was blocked. We showed Arl13bV358A/V358A mice are viable and fertile with normal Shh signal transduction. However, in contrast to wild type cilia, Arl13bV358A/V358A 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.

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Citations

Jun 11, 2020·American Journal of Physiology. Cell Physiology·Skylar FisherElizabeth Sztul
Oct 23, 2020·The Journal of Cell Biology·Ivona MateskaSuzanne Eaton
Jan 1, 2021·Neurobiology of Disease·Abraham Andreu-CerveraSylvie Schneider-Maunoury
Jun 17, 2020·Seminars in Cell & Developmental Biology·Daniel KopinkeSaikat Mukhopadhyay
May 2, 2021·Cell·Melissa E TruongJeremy F Reiter
Jul 12, 2021·Genome Biology and Evolution·Romana VargováMarek Eliáš
Oct 9, 2021·Nature Communications·Shalmali ShuklaPeter Herrlich

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Datasets Mentioned

BETA
AB9610

Methods Mentioned

BETA
GTPases
nucleotide exchange
GTPase
genotyping
Transgenic
PCR

Software Mentioned

GraphPad Prism

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