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LRRK2 functions in synaptic vesicle endocytosis through a kinase-dependent mechanism
Abstract
Mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease, but the precise physiological function of the protein remains ill-defined. Recently, our group proposed a model in which LRRK2 kinase activity is part of an EndoA phosphorylation cycle that facilitates efficient vesicle formation at synapses in the Drosophila melanogaster neuromuscular junctions. Flies harbor only one LRRK gene that may encompass the functions of both mammalian LRRK1 and LRRK2. We therefore studied the role of LRRK2 in mammalian synaptic function and provide evidence that knockout or pharmacological inhibition of LRRK2 results in defects in synaptic vesicle endocytosis, altered synaptic morphology and impairments in neurotransmission. In addition, our data indicate that mammalian endophilin A1 (EndoA1) is phosphorylated by LRRK2 in vitro at T73 and S75, two residues in the BAR domain. Hence, our results indicate that LRRK2 kinase activity has an important role in the regulation of clathrin-mediated endocytosis of synaptic vesicles and subsequent neurotransmission at the synapse.
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LRRK2 localizes to and plays a role in synaptic vesicle trafficking.
“LRRK2 localizes to and plays a role in synaptic vesicle trafficking [2, 10, 13, 49].”
From Cellular and subcellular localization of Rab10 and phospho-T73 Rab10 in the mouse and human brain (2023) · cites this paper as [2]
LRRK2 activity plays a role in synaptic vesicle endocytosis, activation of autophagy, and axonal transport of growth factor receptors.
“LRRK2 activity plays a role in synaptic vesicle endocytosis, activation of autophagy, and axonal transport of growth factor receptors [2, 7, 10, 24, 25, 36, 51, 59, 62, 75, 77, 96].”
From Cellular and subcellular localization of Rab10 and phospho-T73 Rab10 in the mouse and human brain (2023) · cites this paper as [2]
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Metadata
- Authors
- Arranz, A. M., Delbroek, L., Van Kolen, K., Guimarães, M. R., Mandemakers, W., Daneels, G., Matta, S., Calafate, S., Shaban, H., Baatsen, P., De Bock, P.-J., Gevaert, K., Vanden Berghe, P., Verstreken, P., De Strooper, B., & Moechars, D.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2014-01-01
- ISSN
- 1477-9137
- 0021-9533
- Cited by
- 111
- References
- 1
- Language
- en
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