Parkinsonism Sac domain mutation in Synaptojanin-1 affects ciliary properties in iPSC-derived dopaminergic neurons.

ABSTRACT: Synaptojanin-1 (SJ1) is a major neuronal-enriched PI(4,5)P₂ 4- and 5-phosphatase implicated in the shedding of endocytic factors during endocytosis. A mutation (R258Q) that impairs selectively its 4-phosphatase activity causes Parkinsonism in humans and neurological defects in mice (SJ1^RQKI mice). Studies of these mice showed, besides an abnormal assembly state of endocytic factors at synapses, the presence of dystrophic nerve terminals selectively in a subset of nigro-striatal dopamine (DA)-ergic axons, suggesting a special lability of DA neurons to the impairment of SJ1 function. Here we have further investigated the impact of SJ1 on DA neurons using iPSC-derived SJ1 KO and SJ1^RQKI DA neurons and their isogenic controls. In addition to the expected enhanc

SUBMITTER: Rafiq NM 

PROVIDER: S-EPMC10592818 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature