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

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.

The GID ubiquitin ligase complex just reached the next level of complexity.

This issue of Molecular Cell features two publications that make striking discoveries concerning the GID ubiquitin ligase complex. Kong et al. (2021) describe a substrate recognition mechanism, expanding the set of GID complex substrates, whereas Sherpa et al.