A Phosphosite Mutant Approach on LRRK2 Links Phosphorylation and Dephosphorylation to Protective and Deleterious Markers, Respectively
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Plasmids and Stable Cell Lines
2.3. Immunoblotting, Antibodies and Densitometry
2.4. LRRK2 Purification
2.5. In Vitro Kinase Assay
2.6. GTPase Activity
2.7. Protein Stability Assay and Microscale Thermophoresis Analysis
2.8. Immunocytochemistry
2.9. Lysosomal Isolation
2.10. Image Stream Analysis
2.11. Incucyte Live Cell Analysis
2.12. Statistical Analysis
3. Results
3.1. LRRK2 Phosphorylation Is Affected by Its Phosphorylation Mutants
3.2. Heterologous Phosphorylation of LRRK2 Affects Its Autophosphorylation
3.3. In Vitro Assay Is Not Affected by the Phosphorylation Profile of LRRK2
3.4. NGF Induced Neurite Length and Branch Points in PC12 Cells Are Not Affected by Expression of LRRK2 WT or Phosphomutants
3.5. LRRK2 and Its Phosphorylation Mutants Are Localized to the Lysosomes
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Acknowledgments
Conflicts of Interest
References
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Marchand, A.; Sarchione, A.; Athanasopoulos, P.S.; Roy, H.B.-L.; Goveas, L.; Magnez, R.; Drouyer, M.; Emanuele, M.; Ho, F.Y.; Liberelle, M.; et al. A Phosphosite Mutant Approach on LRRK2 Links Phosphorylation and Dephosphorylation to Protective and Deleterious Markers, Respectively. Cells 2022, 11, 1018. https://doi.org/10.3390/cells11061018
Marchand A, Sarchione A, Athanasopoulos PS, Roy HB-L, Goveas L, Magnez R, Drouyer M, Emanuele M, Ho FY, Liberelle M, et al. A Phosphosite Mutant Approach on LRRK2 Links Phosphorylation and Dephosphorylation to Protective and Deleterious Markers, Respectively. Cells. 2022; 11(6):1018. https://doi.org/10.3390/cells11061018
Chicago/Turabian StyleMarchand, Antoine, Alessia Sarchione, Panagiotis S. Athanasopoulos, Hélène Bauderlique-Le Roy, Liesel Goveas, Romain Magnez, Matthieu Drouyer, Marco Emanuele, Franz Y. Ho, Maxime Liberelle, and et al. 2022. "A Phosphosite Mutant Approach on LRRK2 Links Phosphorylation and Dephosphorylation to Protective and Deleterious Markers, Respectively" Cells 11, no. 6: 1018. https://doi.org/10.3390/cells11061018