Neuronal cell type-specific alternative splicing is regulated by the KH domain protein SLM1.
The unique functional properties and molecular identity of neuronal cell populations rely on cell type-specific gene expression programs. Alternative splicing represents a powerful mechanism for expanding the capacity of genomes to generate molecular diversity. Neuronal cells exhibit particularly extensive alternative splicing regulation. We report a highly selective expression of the KH domain-containing splicing regulators SLM1 and SLM2 in the mouse brain. Conditional ablation of SLM1 resulted in a severe defect in the neuronal isoform content of the polymorphic synaptic receptors neurexin-1, -2, and -3. Thus, cell type-specific expression of SLM1 provides a mechanism for shaping the molecular repertoires of synaptic adhesion molecules in neuronal populations in vivo.
Biozentrum, University of Basel, 4056 Basel, Switzerland.
Takatoshi
T
Iijima
Yoko
Y
Iijima
Harald
H
Witte
Peter
P
Scheiffele
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D017930:Genes, Reporter; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009928:Organ Specificity; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C513253:Khdrbs1 protein, mouse; C118776:Khdrbs2 protein, mouse; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins