GORAB makes a novel scaffold for Golgi vesicle trafficking
GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation.
Witkos TM, Chan WL, Joensuu M, Rhiel M, Pallister E, Thomas-Oates J, Mould AP, Mironov AA, Biot C, Guerardel Y, Morelle W, Ungar D, Wieland FT, Jokitalo E, Tassabehji M, Kornak U, Lowe M.
Identifying a novel scaffold for making transport vesicles at the Golgi apparatus comprised of the protein GORAB.
Transport of proteins within the Golgi apparatus, which is essential for the function of the secretory pathway, is mediated by the COPI protein complex.
Here, we identify the coiled-coil protein GORAB, whose mutation causes the skin and bone disorder gerodermia osteodysplastica (GO), as a new component of the COPI machinery.
GORAB forms discrete domains at the Golgi membrane that act as platforms for COPI recruitment. GORAB-mediated COPI recruitment is important for maintaining vesicle transport within the Golgi, which in turn is required to maintain the correct distribution of Golgi enzymes at this organelle.
Loss of GORAB perturbs Golgi enzyme distribution and causes a deficit in the glycosylation of cargo proteins.
Our results provide new insight into how vesicle traffic occurs at the Golgi apparatus, and reveal the mechanistic basis of GO in humans.
- GORAB localises to discrete membrane domains at the Golgi apparatus.
- The GORAB domains scaffold recruitment of the Golgi vesicle coat protein complex COPI.
- GORAB is required to maintain the correct localisation of enzymes within the Golgi apparatus.
- Loss of GORAB causes disrupted cargo protein glycosylation.
- Martin Lowe
- May Tassabehji
- Institute of Medical Genetics and Human Genetics of the Charité Berlin
- University of Helsinki Institute of Biotechnology
- Heidelberg University Biochemistry Centre
- University of York
- University of Lille
- Faculty of 1000 article: GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation.