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

VPS13 proteins are evolutionarily conserved. Mutations in the four human genes (<i>VPS13A-D</i>) encoding VPS13A-D proteins are linked to developmental or neurodegenerative diseases. The relationship between the specific localization of individual VPS13 proteins, their molecular function...

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Autores principales:	Damian Kolakowski, Weronika Rzepnikowska, Aneta Kaniak-Golik, Teresa Zoladek, Joanna Kaminska
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Arf1 Vps13 VPS13A Golgi apparatus mitochondria PH-like domain Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/ca2c3cbb52cd46dea30442b7c63e5868
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spelling	oai:doaj.org-article:ca2c3cbb52cd46dea30442b7c63e58682021-11-25T17:54:56ZThe GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus10.3390/ijms2222122741422-00671661-6596https://doaj.org/article/ca2c3cbb52cd46dea30442b7c63e58682021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12274https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067VPS13 proteins are evolutionarily conserved. Mutations in the four human genes (<i>VPS13A-D</i>) 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 <i>arf1-3 arf2</i>Δ <i>vps13</i>∆ 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.Damian KolakowskiWeronika RzepnikowskaAneta Kaniak-GolikTeresa ZoladekJoanna KaminskaMDPI AGarticleArf1Vps13VPS13AGolgi apparatusmitochondriaPH-like domainBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12274, p 12274 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arf1 Vps13 VPS13A Golgi apparatus mitochondria PH-like domain Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Arf1 Vps13 VPS13A Golgi apparatus mitochondria PH-like domain Biology (General) QH301-705.5 Chemistry QD1-999 Damian Kolakowski Weronika Rzepnikowska Aneta Kaniak-Golik Teresa Zoladek Joanna Kaminska The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus
description	VPS13 proteins are evolutionarily conserved. Mutations in the four human genes (<i>VPS13A-D</i>) 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 <i>arf1-3 arf2</i>Δ <i>vps13</i>∆ 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.
format	article
author	Damian Kolakowski Weronika Rzepnikowska Aneta Kaniak-Golik Teresa Zoladek Joanna Kaminska
author_facet	Damian Kolakowski Weronika Rzepnikowska Aneta Kaniak-Golik Teresa Zoladek Joanna Kaminska
author_sort	Damian Kolakowski
title	The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus
title_short	The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus
title_full	The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus
title_fullStr	The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus
title_full_unstemmed	The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus
title_sort	gtpase arf1 is a determinant of yeast vps13 localization to the golgi apparatus
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ca2c3cbb52cd46dea30442b7c63e5868
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The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus

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