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Can I read Alternative Splicing of Latrophilin-3 Controls Synapse Formation on EtoBox?
Alternative Splicing of Latrophilin-3 Controls Synapse Formation by Shuai Wang; Chelsea DeLeon; Wenfei Sun; Stephen R. Quake; Bryan L. Roth; Thomas C. Südhof is a Physics and Astronomy article available to read on EtoBox.
What is Alternative Splicing of Latrophilin-3 Controls Synapse Formation about?
## 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 hippocampus^4^ 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 Gα~s~- to a Gα~12/13~-coupled mode impaired synaptic connectivity as severely as the overall deletion of __Lphn3__, suggesting that Gα~s~ signalling by LPHN3 splice variants mediates synapse formation. Notably, Gα~s~-coupled, but not Gα~12/13~-coupled, splice variants of LPHN3 also recruit phase-transitioned postsynaptic protein scaffold condensates, such that these condensates are clustered by binding of presynap
Who reads Alternative Splicing of Latrophilin-3 Controls Synapse Formation?
It is typically read by researchers, students, and practitioners in Physics and Astronomy.
- Author
- Shuai Wang; Chelsea DeLeon; Wenfei Sun; Stephen R. Quake; Bryan L. Roth; Thomas C. Südhof
- Publisher
- Nature Publishing Group UK
- Published
- 2024
- Language
- EN
- Field
- Physics and Astronomy (Physical Sciences)