Lysosomal glucocerebrosidase is needed for ciliary Hedgehog signaling: A convergent pathway contributing to Parkinson's disease
Nair SV, Jaimon E, Adhikari A, Nikoloff J, Pfeffer SR. Lysosomal glucocerebrosidase is needed for ciliary Hedgehog signaling: A convergent pathway contributing to Parkinson's disease. Proc Natl Acad Sci U S A. 2025 Aug 5;122(31):e2504774122. doi: 10.1073/pnas.2504774122.
PPM1M, an LRRK2-counteracting, phosphoRab12-preferring phosphatase with a potential link to Parkinson's disease
Chiang CY, Pratuseviciute N, Lin YE, Adhikari A, Yeshaw WM, Flitton C, Sherpa PL, Tonelli F, Rektorova I, Lynch T, Siuda J, Rudzińska-Bar M, Pulyk O, Bauer P, Beetz C, Dickson DW, Ross OA, Wszolek ZK; Global Parkinson’s Genetics Program (GP2); Fang ZH, Klein C, Zimprich A, Alessi DR, Sammler EM, Pfeffer SR. PPM1M, an LRRK2-counteracting, phosphoRab12-preferring phosphatase with a potential link to Parkinson's disease. Cell Rep. 2025 Jul 20;44(8):116031. doi: 10.1016/j.celrep.2025.116031.
Restoration of striatal neuroprotective pathways by kinase inhibitor treatment of Parkinson's disease-linked LRRK2-mutant mice
Jaimon E, Lin YE, Tonelli F, Antico O, Alessi DR, Pfeffer SR. Sci Signal. 2025 Jul;18(893):eads5761. doi: 10.1126/scisignal.ads5761.
Pathogenic LRRK2 mutations cause loss of primary cilia and Neurturin in striatal parvalbumin interneurons
Lin YE, Jaimon E, Tonelli F, Pfeffer SR. Life Sci Alliance. 2024 Nov 13;8(1):e202402922. doi: 10.26508/lsa.202402922.
Localization of PPM1H phosphatase tunes Parkinson’s disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis
Yeshaw WM, Adhikari A, Chiang CY, Dhekne HS, Wawro PS, Pfeffer SR. 2023 Oct 31;120(44):e2315171120. doi: 10.1073/pnas.2315171120.
Genome-wide screen reveals Rab12 GTPase as a critical activator of pathogenic LRRK2 kinase
Dhekne HS, Tonelli F, Yeshaw WM, Chiang CY, Limouse C, Jaimon E, Purlyte E, Alessi DR, Pfeffer SR. Genome-wide screen reveals Rab12 GTPase as a critical activator of Parkinson's disease-linked LRRK2 kinase. Elife. 2023 Oct 24;12:e87098. doi: 10.7554/eLife.87098.
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
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
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.
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
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.
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.
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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.
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.
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.
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.
LRRK2 and Rab GTPases.
Pfeffer SR. Biochem Soc Trans. 2018 Dec 17;46(6):1707-1712. doi: 10.1042/BST20180470. Epub 2018 Nov 22.
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.
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.