MBL-1 and EEL-1 affect the splicing and protein levels of MEC-3 to control dendrite complexity

by Jianxin Xie, Wei Zou, Madina Tugizova, Kang Shen, Xiangming Wang Transcription factors (TFs) play critical roles in specifying many aspects of neuronal cell fate including dendritic morphology. How TFs are accurately regulated during neuronal morphogenesis is not fully understood. Here, we show that LIM homeodomain protein MEC-3, the key TF forC.elegans PVD dendrite morphogenesis, is regulated by both alternative splicing and an E3 ubiquitin ligase. Themec-3 gene generates several transcripts by alternative splicing. We find thatmbl-1, the orthologue of the muscular dystrophy disease gene muscleblind-like (MBNL), is required for PVD dendrite arbor formation. Our data suggestmbl-1 regulates the alternative splicing ofmec-3 to produce its long isoform. Deleting the long isoform ofmec-3(deExon2) causes reduction of dendrite complexity. Through a genetic modifier screen, we find that mutation in the E3 ubiquitin ligase EEL-1 suppressesmbl-1 phenotype.eel-1 mutants also suppressmec-3(deExon2) mutant but not themec-3 null phenotype. Loss of EEL-1 alone leads to excessive dendrite branches. Together, these results indicate that MEC-3 is fine-tuned by alternative splicing and the ubiquitin system to produce the optimal level of dendrite branches.
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research