Protein quality control machinery supports primary ciliogenesis by eliminating GDP-bound Rab8-family GTPases

Toshiki Takahashi; Jun Shirai; Miyo Matsuda; Sae Nakanaga; Shin Matsushita; Kei Wakita; Mizuki Hayashishita; Rigel Suzuki; Aya Noguchi; Naoto Yokota; Hiroyuki Kawahara

doi:10.1016/j.isci.2023.106652

Protein quality control machinery supports primary ciliogenesis by eliminating GDP-bound Rab8-family GTPases

iScience. 2023 Apr 10;26(5):106652. doi: 10.1016/j.isci.2023.106652. eCollection 2023 May 19.

Authors

Affiliation

¹ Laboratory of Cell Biology and Biochemistry, Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan.

Abstract

The small GTPase Rab8 plays a vital role in the vesicular trafficking of cargo proteins from the trans-Golgi network to target membranes. Upon reaching its target destination, Rab8 is released from the vesicular membrane into the cytoplasm via guanosine triphosphate (GTP) hydrolysis. The fate of GDP-bound Rab8 released from the destination membranes, however, has not been investigated adequately. In this study, we found that GDP-bound Rab8 subfamily proteins are targeted for immediate degradation, and the pre-emptive quality control machinery is responsible for eliminating these proteins in a nucleotide-specific manner. We provide evidence that components of this quality control machinery have a critical role in vesicular trafficking events, including the formation of primary cilia, a process regulated by the Rab8 subfamily. These results suggest that the protein degradation machinery plays a critical role in the integrity of membrane trafficking by limiting the excessive accumulation of GDP-bound Rab8 subfamily proteins.

Keywords: Cell biology; Molecular biology.