Article
Lysosomal TPC2 channels disrupt Ca2+ entry and dopaminergic function in models of LRRK2-Parkinson's disease.
The Journal of cell biology - 2 Jun 2025
Gregori Martina, Pereira Gustavo J S, Allen Robert, West Nicholas, Chau Kai-Yin, Cai Xinjiang, Bostock Matthew P, Bolsover Stephen R, Keller Marco, Lee Chiao-Yin, Lei Si Hang, Harvey Kirsten, Bracher Franz, Grimm Christian, Hasan Gaiti, Gegg Matthew E, Schapira Anthony H V, Sweeney Sean T, Patel Sandip
Abstract excerpt
Parkinson's disease results from degeneration of dopaminergic neurons in the midbrain, but the underlying mechanisms are unclear. Here, we identify novel crosstalk between depolarization-induced entry of Ca2+ and lysosomal cation release in maintaining dopaminergic neuronal function. The common disease-causing G2019S mutation in LRRK2 selectively exaggerated Ca2+ entry in vitro. Chemical and molecular strategies...
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