Chloe Flitton
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Chloe Flitton has a total of 33 co-authors. Here are the top co-authors by number of shared publications:
Achim Paululat
Department of Zoology & Developmental Biology, Osnabrück University, 49076 Osnabrück, Germany
1 shared publication- Alexander Zimprich
Department of Neurology, Medical University of Vienna, Vienna 1090, Austria
1 shared publication - Andrea Raimondi
Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland
1 shared publication - Ayan Adhikari
Department of Biochemistry, Stanford University School of Medicine
1 shared publication Bhavya Sivalingam
Division of Molecular Membrane Biology, Department of Biology/Chemistry, Osnabrück University, 49076 Osnabrück, Germany
1 shared publication- Christian Beetz
Centogene GmbH, Rostock, Germany
1 shared publication
Latest Publications
- Open Access
PPM1M, a LRRK2-counteracting, phosphoRab12-preferring phosphatase with potential link to Parkinson’s disease
Leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of Rab GTPases that regulate receptor trafficking; activating mutations in LRRK2 are linked to Parkinson’s disease. Rab phosphorylation is a transient event that can be reversed by phosphatases, including PPM1H, that acts on phosphoRab8A and phosphoRab10. Here we report a phosphatome-wide siRNA screen that identified PPM1M as a phosphoRab12-preferring phosphatase that also acts on phosphoRab8A and phosphoRab10. Upon knockout from cells or mice, PPM1M displays selectivity for phosphoRab12. As shown previously for mice harboring LRRK2 pathway mutations, knockout of Ppm1m leads to primary cilia loss in striatal cholinergic interneurons. We have also identified a rare PPM1M mutation in patients with Parkinson’s disease that is catalytically inactive when tested in vitro and in cells. These findings identify PPM1M as a key player in the LRRK2 signaling pathway and provide a new therapeutic target for the possible benefit of patients with Parkinson’s disease. Teaser: Parkinson’s linked Rab phosphorylation is reversed by PPM1M; the inactive D440N variant is implicated in rare patient cases.
Open AccessPPM1M, a LRRK2-counteracting, phosphoRab12-preferring phosphatase with potential link to Parkinson’s disease
Leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of Rab GTPases that regulate receptor trafficking; activating mutations in LRRK2 are linked to Parkinson’s disease. Rab phosphorylation is a transient event that can be reversed by phosphatases, including PPM1H, that acts on phosphoRab8A and phosphoRab10. Here we report a phosphatome-wide siRNA screen that identified PPM1M as a phosphoRab12-preferring phosphatase that also acts on phosphoRab8A and phosphoRab10. Upon knockout from cells or mice, PPM1M displays selectivity for phosphoRab12. As shown previously for mice harboring LRRK2 pathway mutations, knockout of Ppm1m leads to primary cilia loss in striatal cholinergic interneurons. We have also identified a rare PPM1M mutation in patients with Parkinson’s disease that is catalytically inactive when tested in vitro and in cells. These findings identify PPM1M as a key player in the LRRK2 signaling pathway and provide a new therapeutic target for the possible benefit of patients with Parkinson’s disease. Teaser: Parkinson’s linked Rab phosphorylation is reversed by PPM1M; the inactive D440N variant is implicated in rare patient cases.
- Open Access
- 3 January 2025
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 11 (1) , eadr7325
RpH-ILV: Probe for lysosomal pH and acute LLOMe-induced membrane permeabilization in cell lines and Drosophila
Lysosomal pH dysregulation is a critical element of the pathophysiology of neurodegenerative diseases, cancers, and lysosomal storage disorders (LSDs). To study the role of lysosomes in pathophysiology, probes to analyze lysosomal size, positioning, and pH are indispensable tools. Here, we developed and characterized a ratiometric genetically encoded lysosomal pH probe, RpH-ILV, targeted to a subpopulation of lysosomal intraluminal vesicles. This subpopulation behaves similarly to the general population of LAMP1-positive vesicles in terms of pH response to pharmacological stresses. In addition, RpH-ILV, which is trafficked to the lysosome via a different cytosolic motif than our previous ratiometric sensor, RpH-LAMP1, is well tolerated by the model organism Drosophila melanogaster , exhibits minimal plasma membrane fluorescence, and reveals sensitivity to the lysosomal damaging agent LLOMe, adding a valuable tool to our repertoire of lysosomal pH sensors.
- 3 January 2025
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 11 (1) , eadr7325
Open AccessRpH-ILV: Probe for lysosomal pH and acute LLOMe-induced membrane permeabilization in cell lines and Drosophila
Lysosomal pH dysregulation is a critical element of the pathophysiology of neurodegenerative diseases, cancers, and lysosomal storage disorders (LSDs). To study the role of lysosomes in pathophysiology, probes to analyze lysosomal size, positioning, and pH are indispensable tools. Here, we developed and characterized a ratiometric genetically encoded lysosomal pH probe, RpH-ILV, targeted to a subpopulation of lysosomal intraluminal vesicles. This subpopulation behaves similarly to the general population of LAMP1-positive vesicles in terms of pH response to pharmacological stresses. In addition, RpH-ILV, which is trafficked to the lysosome via a different cytosolic motif than our previous ratiometric sensor, RpH-LAMP1, is well tolerated by the model organism Drosophila melanogaster , exhibits minimal plasma membrane fluorescence, and reveals sensitivity to the lysosomal damaging agent LLOMe, adding a valuable tool to our repertoire of lysosomal pH sensors.