LRRK2 links endocytosis to Parkinson’s disease
Defects in endocytosis and mutations in the kinase LRRK2 are associated with Parkinson’s disease. Liu et al. found that LRRK2 directly regulates endocytosis by phosphorylating a protein critical to clathrin coating and uncoating cycles. In cultured neurons and animal models, LRRK2-mediated phosphorylation of the AP2 complex subunit M1 was essential for initiating clathrin coating of budding endocytic vesicles. However, increased activation of LRRK2—such as that caused by a Parkinson’s disease–associated mutation—prevented the uncoating of AP2M1 after internalization, thereby impairing endocytic trafficking. This effect was implicated in the loss of dopaminergic neurons in a fly model of LRRK2-mutant PD, suggesting that it may underlie pathology in patients.
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July 28, 2021 at 01:04AM
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Dysregulation of the AP2M1 phosphorylation cycle by LRRK2 impairs endocytosis and leads to dopaminergic neurodegeneration - Science
"cycle" - Google News
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