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Localization of PPM1H phosphatase tunes Parkinson’s disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis

Wondwossen M. Yeshaw, Ayan Adhikari, Claire Y. Chiang, Herschel S. Dhekne, Paulina S. Wawro, Suzanne R. Pfeffer. 2023 Oct 31;120(44):e2315171120. doi: 10.1073/pnas.2315171120.

PDF | PMID: 37889931


Genome-wide screen reveals Rab12 GTPase as a critical activator of pathogenic LRRK2 kinase

Herschel S. Dhekne, Francesca Tonelli, Wondwossen M. Yeshaw, Claire Y. Chiang, Charles Limouse, Ebsy Jaimon, ElenaPurlyte, Dario R. Alessi, Suzanne R. Pfeffer. bioRxiv 2023.02.17.529028; doi: https://doi.org/10.1101/2023.02.17.529028. eLIFE IN PRESS.


A feed-forward pathway drives LRRK2 kinase membrane recruitment and activation
Vides EG, Adhikari A, Chiang CY, Lis P, Purlyte E, Limouse C, Shumate JL, Spínola-Lasso E, Dhekne HS, Alessi DR, & Pfeffer SR (2022). eLife, 11, e79771. doi:10.7554/eLife.79771

PDF | PMID: 36149401


CRISPR screens for lipid regulators reveal a role for ER-bound SNX13 in lysosomal cholesterol export
Lu A, Hsieh F, Sharma BR, Vaughn SR, Enrich C, & Pfeffer SR (2022).  The Journal of cell biology, 221(2), e202105060. doi: 10.1083/jcb.202105060

PDF | PMID: 34936700


Pathogenic LRRK2 control of primary cilia and Hedgehog signaling in neurons and astrocytes of mouse brain
Khan SS, Sobu Y, Dhekne HS, Tonelli F, Berndsen K, Alessi DR, Pfeffer SR.  eLife. 2021 Oct 18;10:e67900. doi: 10.7554/eLife.67900.

PDF | PMID: 34658337


Rab29 Fast Exchange Mutants: Characterization of a Challenging Rab GTPase
Gomez RC, Vides EG, Pfeffer SR.  MethodMol Biol. 2021;2293:19-25. doi: 10.1007/978-1-0716-1346-7_2

PDF | PMID: 34453707


LRRK2-phosphorylated Rab10 sequesters Myosin Va with RILPL2 during ciliogenesis blockade.
Dhekne HS, Yanatori I, Vides EG, Sobu Y, Diez F, Tonelli F, Pfeffer SR.  Life Sci Alliance. 2021 Mar 16;4(5):e202101050. doi: 10.26508/lsa.202101050.

PDF | PMID: 33727250


Pathogenic LRRK2 regulates ciliation probability upstream of tau tubulin kinase 2 via Rab 10 and RILPL1 proteins.
Sobu Y, Wawro PS, Dhekne HS, Yeshaw WM, Pfeffer SR. Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):e2005894118. doi: 10.1073/pnas.2005894118.

PDF | PMID: 3365948


Inter-domain dynamics drive cholesterol transport by NPC1 and NPC1L1 proteins.
Saha P, Shumate JL, Caldwell JG, Elghobashi-Meinhardt N, Lu A, Zhang L, Olsson NE, Elias JE, Pfeffer SR. Elife. 2020 May 15;9:e57089. doi: 10.7554/eLife.57089.

PDF | PMID: 32410728


PPM1H phosphatase counteracts LRRK2 signaling by selectively dephosphorylating Rab proteins.
Berndsen K, Lis P, Yeshaw WM, Wawro PS, Nirujogi RS, Wightman M, Macartney T, Dorward M, Knebel A, Tonelli F, Pfeffer SR, Alessi DR. Elife. 2019 Oct 30;8:e50416. doi: 10.7554/eLife.50416.

PDF | PMID: 31663853

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Membrane association but not identity is required for LRRK2 activation and phosphorylation of Rab GTPases.
Gomez RC, Wawro P, Lis P, Alessi DR, Pfeffer SR. J Cell Biol. 2019 Dec 2;218(12):4157-4170. doi: 10.1083/jcb.201902184. Epub 2019 Oct 17.

PDF | PMID: 31624137

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Genome-wide interrogation of extracellular vesicle biology using barcoded miRNAs.
Lu A, Wawro P, Morgens DW, Portela F, Bassik MC, Pfeffer SR. Elife 2018 Dec 17;7:e41460. doi: 10.7554/eLife.41460.

PDF | PMID: 30556811

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LRRK2 and Rab GTPases.
Pfeffer SR
. Biochem Soc Trans. 2018 Dec 17;46(6):1707-1712. doi: 10.1042/BST20180470. Epub 2018 Nov 22.

PDF | PMID: 30467121

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A pathway for Parkinson’s Disease LRRK2 kinase to block primary cilia and Sonic hedgehog signaling in the brain.
Dhekne HS, Yanatori I, Gomez RC, Tonelli F, Diez F, Schüle B, Steger M, Alessi DR, Pfeffer SR. Elife 2018 Nov 6;7:e40202. doi: 10.7554/eLife.40202.

PDF | PMID: 30398148

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Rab29 activation of the Parkinson's disease-associated LRRK2 kinase.
Purlyte E, Dhekne HS, Sarhan AR, Gomez R, Lis P, Wightman M, Martinez TN, Tonelli F, Pfeffer SR, Alessi DR. EMBO J. 2018 Jan 4;37(1):1-18. doi: 10.15252/embj.201798099. Epub 2017 Dec 6.

PDF | PMID: 29212815