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Localization of PPM1H phosphatase tunes Parkinson’s disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis
PPM1H phosphatase reverses Parkinson’s disease-associated, Leucine Rich Repeat Kinase 2-mediated Rab GTPase phosphorylation. We show here that PPM1H relies on an N-terminal amphipathic helix for Golgi localization. The amphipathic helix enables PPM1H to bind to liposomes in vitro, and small, highly...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10622911/ https://www.ncbi.nlm.nih.gov/pubmed/37889931 http://dx.doi.org/10.1073/pnas.2315171120 |
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author | Yeshaw, Wondwossen M. Adhikari, Ayan Chiang, Claire Y. Dhekne, Herschel S. Wawro, Paulina S. Pfeffer, Suzanne R. |
author_facet | Yeshaw, Wondwossen M. Adhikari, Ayan Chiang, Claire Y. Dhekne, Herschel S. Wawro, Paulina S. Pfeffer, Suzanne R. |
author_sort | Yeshaw, Wondwossen M. |
collection | PubMed |
description | PPM1H phosphatase reverses Parkinson’s disease-associated, Leucine Rich Repeat Kinase 2-mediated Rab GTPase phosphorylation. We show here that PPM1H relies on an N-terminal amphipathic helix for Golgi localization. The amphipathic helix enables PPM1H to bind to liposomes in vitro, and small, highly curved liposomes stimulate PPM1H activity. We artificially anchored PPM1H to the Golgi, mitochondria, or mother centriole. Our data show that regulation of Rab10 GTPase phosphorylation requires PPM1H access to Rab10 at or near the mother centriole. Moreover, poor colocalization of Rab12 explains in part why it is a poor substrate for PPM1H in cells but not in vitro. These data support a model in which localization drives PPM1H substrate selection and centriolar PPM1H is critical for regulation of Rab GTPase-regulated ciliogenesis. Moreover, Golgi localized PPM1H may maintain active Rab GTPases on the Golgi to carry out their nonciliogenesis-related functions in membrane trafficking. |
format | Online Article Text |
id | pubmed-10622911 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-106229112023-11-04 Localization of PPM1H phosphatase tunes Parkinson’s disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis Yeshaw, Wondwossen M. Adhikari, Ayan Chiang, Claire Y. Dhekne, Herschel S. Wawro, Paulina S. Pfeffer, Suzanne R. Proc Natl Acad Sci U S A Biological Sciences PPM1H phosphatase reverses Parkinson’s disease-associated, Leucine Rich Repeat Kinase 2-mediated Rab GTPase phosphorylation. We show here that PPM1H relies on an N-terminal amphipathic helix for Golgi localization. The amphipathic helix enables PPM1H to bind to liposomes in vitro, and small, highly curved liposomes stimulate PPM1H activity. We artificially anchored PPM1H to the Golgi, mitochondria, or mother centriole. Our data show that regulation of Rab10 GTPase phosphorylation requires PPM1H access to Rab10 at or near the mother centriole. Moreover, poor colocalization of Rab12 explains in part why it is a poor substrate for PPM1H in cells but not in vitro. These data support a model in which localization drives PPM1H substrate selection and centriolar PPM1H is critical for regulation of Rab GTPase-regulated ciliogenesis. Moreover, Golgi localized PPM1H may maintain active Rab GTPases on the Golgi to carry out their nonciliogenesis-related functions in membrane trafficking. National Academy of Sciences 2023-10-27 2023-10-31 /pmc/articles/PMC10622911/ /pubmed/37889931 http://dx.doi.org/10.1073/pnas.2315171120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Biological Sciences Yeshaw, Wondwossen M. Adhikari, Ayan Chiang, Claire Y. Dhekne, Herschel S. Wawro, Paulina S. Pfeffer, Suzanne R. Localization of PPM1H phosphatase tunes Parkinson’s disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis |
title | Localization of PPM1H phosphatase tunes Parkinson’s disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis |
title_full | Localization of PPM1H phosphatase tunes Parkinson’s disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis |
title_fullStr | Localization of PPM1H phosphatase tunes Parkinson’s disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis |
title_full_unstemmed | Localization of PPM1H phosphatase tunes Parkinson’s disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis |
title_short | Localization of PPM1H phosphatase tunes Parkinson’s disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis |
title_sort | localization of ppm1h phosphatase tunes parkinson’s disease-linked lrrk2 kinase-mediated rab gtpase phosphorylation and ciliogenesis |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10622911/ https://www.ncbi.nlm.nih.gov/pubmed/37889931 http://dx.doi.org/10.1073/pnas.2315171120 |
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