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
Affiliations
Toshiki Takahashi
Laboratory of Cell Biology and Biochemistry, Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan
Jun Shirai
Laboratory of Cell Biology and Biochemistry, Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan
Miyo Matsuda
Laboratory of Cell Biology and Biochemistry, Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan
Sae Nakanaga
Laboratory of Cell Biology and Biochemistry, Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan
Shin Matsushita
Laboratory of Cell Biology and Biochemistry, Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan
Kei Wakita
Laboratory of Cell Biology and Biochemistry, Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan
Mizuki Hayashishita
Laboratory of Cell Biology and Biochemistry, Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan
Rigel Suzuki
Laboratory of Cell Biology and Biochemistry, Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan
Aya Noguchi
Laboratory of Cell Biology and Biochemistry, Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan
Naoto Yokota
Laboratory of Cell Biology and Biochemistry, Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan
Hiroyuki Kawahara
Laboratory of Cell Biology and Biochemistry, Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan; Corresponding author
Summary: 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.
