Alternative splicing of latrophilin-3 controls synapse formation.

ABSTRACT: The assembly and specification of synapses in the brain is incompletely understood^1-3. Latrophilin-3 (encoded by Adgrl3, also known as Lphn3)-a postsynaptic adhesion G-protein-coupled receptor-mediates synapse formation in the hippocampus⁴ but the mechanisms involved remain unclear. Here we show in mice that LPHN3 organizes synapses through a convergent dual-pathway mechanism: activation of Gα_s signalling and recruitment of phase-separated postsynaptic protein scaffolds. We found that cell-type-specific alternative splicing of Lphn3 controls the LPHN3 G-protein-coupling mode, resulting in LPHN3 variants that predominantly signal through Gα_s or Gα_12/13. CRISPR-mediated manipulation of Lphn3 alternative splicing that shifts LPHN3 from a

SUBMITTER: Wang S 

PROVIDER: S-EPMC10830413 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature