A cell-type-specific alternative splicing regulator shapes synapse properties in a trans-synaptic manner

Traunmüller, Lisa and Schulz, Jan and Ortiz, Raul and Feng, Huijuan and Furlanis, Elisabetta and Gomez, Andrea M. and Schreiner, Dietmar and Bischofberger, Josef and Zhang, Chaolin and Scheiffele, Peter. (2023) A cell-type-specific alternative splicing regulator shapes synapse properties in a trans-synaptic manner. Cell reports, 42 (3). p. 112173.

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Official URL: https://edoc.unibas.ch/94157/

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The specification of synaptic properties is fundamental for the function of neuronal circuits. "Terminal selector" transcription factors coordinate terminal gene batteries that specify cell-type-specific properties. Moreover, pan-neuronal splicing regulators have been implicated in directing neuronal differentiation. However, the cellular logic of how splicing regulators instruct specific synaptic properties remains poorly understood. Here, we combine genome-wide mapping of mRNA targets and cell-type-specific loss-of-function studies to uncover the contribution of the RNA-binding protein SLM2 to hippocampal synapse specification. Focusing on pyramidal cells and somatostatin (SST)-positive GABAergic interneurons, we find that SLM2 preferentially binds and regulates alternative splicing of transcripts encoding synaptic proteins. In the absence of SLM2, neuronal populations exhibit normal intrinsic properties, but there are non-cell-autonomous synaptic phenotypes and associated defects in a hippocampus-dependent memory task. Thus, alternative splicing provides a critical layer of gene regulation that instructs specification of neuronal connectivity in a trans-synaptic manner.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Cell Biology (Scheiffele)
UniBasel Contributors:Traunmüller, Lisa and Furlanis, Elisabetta and Schreiner, Dietmar and Scheiffele, Peter
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:28 Mar 2023 10:33
Deposited On:28 Mar 2023 10:33

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