Cilia-localized GID/CTLH ubiquitin ligase complex regulates protein homeostasis of sonic hedgehog signaling components.

ABSTRACT: Cilia are evolutionarily conserved organelles that orchestrate a variety of signal transduction pathways, such as sonic hedgehog (SHH) signaling, during embryonic development. Our recent studies have shown that loss of GID ubiquitin ligase function results in aberrant AMP-activated protein kinase (AMPK) activation and elongated primary cilia, which suggests a functional connection to cilia. Here, we reveal that the GID complex is an integral part of the cilium required for primary cilia-dependent signal transduction and the maintenance of ciliary protein homeostasis. We show that GID complex subunits localize to cilia in both Xenopus laevis and NIH3T3 cells. Furthermore, we report SHH signaling pathway defects that are independent of AMPK and mechanistic target of rapamycin (MTOR) activati

SUBMITTER: Hantel F 

PROVIDER: S-EPMC9264362 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature