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Genetic Dissection of Vps13 Regulation in Yeast Using Disease Mutations from Human Orthologs
Article

The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus

1
Institute of Biochemistry and Biophysics, Polish Academy of Science, 02-106 Warsaw, Poland
2
Neuromuscular Unit, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Ian Macreadie
Int. J. Mol. Sci. 2021, 22(22), 12274; https://doi.org/10.3390/ijms222212274
Received: 13 October 2021 / Revised: 8 November 2021 / Accepted: 10 November 2021 / Published: 12 November 2021
VPS13 proteins are evolutionarily conserved. Mutations in the four human genes (VPS13A-D) encoding VPS13A-D proteins are linked to developmental or neurodegenerative diseases. The relationship between the specific localization of individual VPS13 proteins, their molecular functions, and the pathology of these diseases is unknown. Here we used a yeast model to establish the determinants of Vps13′s interaction with the membranes of Golgi apparatus. We analyzed the different phenotypes of the arf1-3 arf2Δ vps13∆ strain, with reduced activity of the Arf1 GTPase, the master regulator of Golgi function and entirely devoid of Vps13. Our analysis led us to propose that Vps13 and Arf1 proteins cooperate at the Golgi apparatus. We showed that Vps13 binds to the Arf1 GTPase through its C-terminal Pleckstrin homology (PH)-like domain. This domain also interacts with phosphoinositol 4,5-bisphosphate as it was bound to liposomes enriched with this lipid. The homologous domain of VPS13A exhibited the same behavior. Furthermore, a fusion of the PH-like domain of Vps13 to green fluorescent protein was localized to Golgi structures in an Arf1-dependent manner. These results suggest that the PH-like domains and Arf1 are determinants of the localization of VPS13 proteins to the Golgi apparatus in yeast and humans. View Full-Text
Keywords: Arf1; Vps13; VPS13A; Golgi apparatus; mitochondria; PH-like domain; PI(4,5)P2; yeast Arf1; Vps13; VPS13A; Golgi apparatus; mitochondria; PH-like domain; PI(4,5)P2; yeast
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MDPI and ACS Style

Kolakowski, D.; Rzepnikowska, W.; Kaniak-Golik, A.; Zoladek, T.; Kaminska, J. The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus. Int. J. Mol. Sci. 2021, 22, 12274. https://doi.org/10.3390/ijms222212274

AMA Style

Kolakowski D, Rzepnikowska W, Kaniak-Golik A, Zoladek T, Kaminska J. The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus. International Journal of Molecular Sciences. 2021; 22(22):12274. https://doi.org/10.3390/ijms222212274

Chicago/Turabian Style

Kolakowski, Damian, Weronika Rzepnikowska, Aneta Kaniak-Golik, Teresa Zoladek, and Joanna Kaminska. 2021. "The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus" International Journal of Molecular Sciences 22, no. 22: 12274. https://doi.org/10.3390/ijms222212274

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