PD-linked LRRK2 G2019S mutation impairs astrocyte morphology and synapse maintenance via ERM hyperphosphorylation.

ABSTRACT: Astrocytes are highly complex cells that mediate critical roles in synapse formation and maintenance by establishing thousands of direct contacts with synapses through their perisynaptic processes. Here, we found that the most common Parkinsonism gene mutation, LRRK2 G2019S, enhances the phosphorylation of the ERM proteins (Ezrin, Radixin, and Moesin), components of the perisynaptic astrocyte processes in a subset of cortical astrocytes. The ERM hyperphosphorylation was accompanied by decreased astrocyte morphological complexity and reduced excitatory synapse density and function. Dampening ERM phosphorylation levels in LRRK2 G2019S mouse astrocytes restored both their morphology and the excitatory synapse density in the anterior cingulate cortex. To determine how LRRK2 mutation impacts Ez

SUBMITTER: Wang S 

PROVIDER: S-EPMC11383028 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature