The role of (auto)-phosphorylation in the complex activation mechanism of LRRK2
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Panagiotis S. Athanasopoulos
Panagiotis S. Athanasopoulos studied Biochemistry and Biotechnology at the University of Thessaly, Greece, in a Diploma program. Then he moved to Utrecht, the Netherlands, for his Master’s degree in Biomolecular Sciences. After that he pursued his PhD in the lab of Prof Dr. Rolf Heumann, in Ruhr University Bochum, Germany. His PhD studies were focused on hereditary Parkinson’s disease (PD). Currently he his working in the lab of Dr. Arjan Kortholt, where he continues to work as a postdoctoral fellow on the same project as his PhD topic.
Rolf Heumann joined the Max-Planck-Institute for Biochemistry/Martinsried to perform his diploma/PhD thesis projects in the field of cellular neuroscience after studying Microbiology at the Technical University of Munich and the Queen Elizabeth College in London. In 1979, he continued as a research assistant at the Max-Planck-Institute for Psychiatry in Martinsried exploring molecular mechanisms of neuronal regeneration and advancing the field of intracellular signaling mechanisms of neurotrophic factors in the brain. In 1991, he was appointed to the Chair holder of the Department of Biochemistry-Molecular Neurobiochemistry in the Faculty for Chemistry and Biochemistry at the Ruhr-University of Bochum. In 2012 he retired from the Department Chair and was appointed as a Senior Professor at the Ruhr-University being responsible for the FET-open Horizon 2020 project MAGNEURON, where he has worked to date.
Arjan Kortholt studied Chemistry and received his PhD degree from the University of Groningen in 2009. In 2007 he started working on the biochemical and structural characterization of small G-proteins in the laboratory of Dr. Wittinghofer (MPI Dortmund). Since 2010 he has been working at the University of Groningen, where he holds a position as Associate Professor. The primary aim of his current research is therapeutic targeting of LRRK2-mediated Parkinson’s disease by elucidating the structure, activation mechanism and function of LRRK2 and related Roco family proteins.
Abstract
Mutations in human leucine-rich-repeat kinase 2 (LRRK2) have been found to be the most frequent cause of late-onset Parkinson’s Disease (PD). LRRK2 is a large protein with two enzymatic domains, a GTPase and a kinase domain. A cluster of (auto)-phosphorylation sites within the N-terminus of LRRK2 have been shown to be crucial for the localization of LRRK2 and is important for PD pathogenesis. In addition, phosphorylation of sites within the G-domain of the protein affect GTPase activity. Here we discuss the role of these (auto)-phosphorylation sites of LRRK2 and their regulation by phosphatases and upstream kinases.
About the authors
Panagiotis S. Athanasopoulos studied Biochemistry and Biotechnology at the University of Thessaly, Greece, in a Diploma program. Then he moved to Utrecht, the Netherlands, for his Master’s degree in Biomolecular Sciences. After that he pursued his PhD in the lab of Prof Dr. Rolf Heumann, in Ruhr University Bochum, Germany. His PhD studies were focused on hereditary Parkinson’s disease (PD). Currently he his working in the lab of Dr. Arjan Kortholt, where he continues to work as a postdoctoral fellow on the same project as his PhD topic.
Rolf Heumann joined the Max-Planck-Institute for Biochemistry/Martinsried to perform his diploma/PhD thesis projects in the field of cellular neuroscience after studying Microbiology at the Technical University of Munich and the Queen Elizabeth College in London. In 1979, he continued as a research assistant at the Max-Planck-Institute for Psychiatry in Martinsried exploring molecular mechanisms of neuronal regeneration and advancing the field of intracellular signaling mechanisms of neurotrophic factors in the brain. In 1991, he was appointed to the Chair holder of the Department of Biochemistry-Molecular Neurobiochemistry in the Faculty for Chemistry and Biochemistry at the Ruhr-University of Bochum. In 2012 he retired from the Department Chair and was appointed as a Senior Professor at the Ruhr-University being responsible for the FET-open Horizon 2020 project MAGNEURON, where he has worked to date.
Arjan Kortholt studied Chemistry and received his PhD degree from the University of Groningen in 2009. In 2007 he started working on the biochemical and structural characterization of small G-proteins in the laboratory of Dr. Wittinghofer (MPI Dortmund). Since 2010 he has been working at the University of Groningen, where he holds a position as Associate Professor. The primary aim of his current research is therapeutic targeting of LRRK2-mediated Parkinson’s disease by elucidating the structure, activation mechanism and function of LRRK2 and related Roco family proteins.
Acknowledgments
We have received funding from the Michael J. Fox Foundation for Parkinson’s Research. RH was funded by HORIZON 2020, Nr 686841.
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©2018 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Highlight Issue ‘Molecular Basis of Life 2017’
- HIGHLIGHT: GBM Fall Meeting “Molecular Basis of Life 2017”
- Neuronal RNP granules: from physiological to pathological assemblies
- Regulation of LRRK2: insights from structural and biochemical analysis
- The role of (auto)-phosphorylation in the complex activation mechanism of LRRK2
- Oncogenic BRAFV600E drives expression of MGL ligands in the colorectal cancer cell line HT29 through N-acetylgalactosamine-transferase 3
- Hypoxia and serum deprivation induces glycan alterations in triple negative breast cancer cells
- Targeting autophagy for the treatment of cancer
- From molecules to patients: exploring the therapeutic role of soluble guanylate cyclase stimulators
- DNA-encoded libraries – an efficient small molecule discovery technology for the biomedical sciences
- Transcytosis of payloads that are non-covalently complexed to bispecific antibodies across the hCMEC/D3 blood-brain barrier model
- Mitochondrial contributions to neuronal development and function
- Intracellular communication between lipid droplets and peroxisomes: the Janus face of PEX19
- Protein crystallization in living cells
- Synthetic DNA filaments: from design to applications
- Spectroscopic characterization of the Co-substituted C-terminal domain of rubredoxin-2
- Twitch or swim: towards the understanding of prokaryotic motion based on the type IV pilus blueprint
Articles in the same Issue
- Frontmatter
- Highlight Issue ‘Molecular Basis of Life 2017’
- HIGHLIGHT: GBM Fall Meeting “Molecular Basis of Life 2017”
- Neuronal RNP granules: from physiological to pathological assemblies
- Regulation of LRRK2: insights from structural and biochemical analysis
- The role of (auto)-phosphorylation in the complex activation mechanism of LRRK2
- Oncogenic BRAFV600E drives expression of MGL ligands in the colorectal cancer cell line HT29 through N-acetylgalactosamine-transferase 3
- Hypoxia and serum deprivation induces glycan alterations in triple negative breast cancer cells
- Targeting autophagy for the treatment of cancer
- From molecules to patients: exploring the therapeutic role of soluble guanylate cyclase stimulators
- DNA-encoded libraries – an efficient small molecule discovery technology for the biomedical sciences
- Transcytosis of payloads that are non-covalently complexed to bispecific antibodies across the hCMEC/D3 blood-brain barrier model
- Mitochondrial contributions to neuronal development and function
- Intracellular communication between lipid droplets and peroxisomes: the Janus face of PEX19
- Protein crystallization in living cells
- Synthetic DNA filaments: from design to applications
- Spectroscopic characterization of the Co-substituted C-terminal domain of rubredoxin-2
- Twitch or swim: towards the understanding of prokaryotic motion based on the type IV pilus blueprint
