| First Author | Hauser D | Year | 2022 |
| Journal | Neuron | Volume | 110 |
| Issue | 13 | Pages | 2094-2109.e10 |
| PubMed ID | 35550065 | Mgi Jnum | J:346431 |
| Mgi Id | MGI:7314107 | Doi | 10.1016/j.neuron.2022.04.017 |
| Citation | Hauser D, et al. (2022) Targeted proteoform mapping uncovers specific Neurexin-3 variants required for dendritic inhibition. Neuron 110(13):2094-2109.e10 |
| abstractText | The diversification of cell adhesion molecules by alternative splicing is proposed to underlie molecular codes for neuronal wiring. Transcriptomic approaches mapped detailed cell-type-specific mRNA splicing programs. However, it has been hard to probe the synapse-specific localization and function of the resulting protein splice isoforms, or "proteoforms," in vivo. We here apply a proteoform-centric workflow in mice to test the synapse-specific functions of the splice isoforms of the synaptic adhesion molecule Neurexin-3 (NRXN3). We uncover a major proteoform, NRXN3 AS5, that is highly expressed in GABAergic interneurons and at dendrite-targeting GABAergic terminals. NRXN3 AS5 abundance significantly diverges from Nrxn3 mRNA distribution and is gated by translation-repressive elements. Nrxn3 AS5 isoform deletion results in a selective impairment of dendrite-targeting interneuron synapses in the dentate gyrus without affecting somatic inhibition or glutamatergic perforant-path synapses. This work establishes cell- and synapse-specific functions of a specific neurexin proteoform and highlights the importance of alternative splicing regulation for synapse specification. |
