Knockout of zebrafish desmin genes does not cause skeletal muscle degeneration but alters calcium flux.

Desmin is a muscle-specific intermediate filament protein that has fundamental role in muscle structure and force transmission. Whereas human desmin protein is encoded by a single gene, two desmin paralogs (desma and desmb) exist in zebrafish. Desma and desmb show differential spatiotemporal expression during zebrafish embryonic and larval development, being similarly expressed in skeletal muscle until hatching, after which expression of desmb shifts to gut smooth muscle. We generated knockout (KO) mutant lines carrying loss-of-function mutations for each gene by using CRISPR/Cas9. Mutants are viable and fertile, and lack obvious skeletal muscle, heart or intestinal defects. In contrast to morphants, knockout of each gene did not cause any overt muscular phenotype, but did alter calcium flux in myofibres. These results point to a possible compensation mechanism in these mutant lines generated by targeting nonsense mutations to the first coding exon.

A cytoplasmic escapee: desmin is going nuclear.

It has been a long time since researchers have focused on the cytoskeletal proteins' unconventional functions in the nucleus. Subcellular localization of a protein not only affects its functions but also determines the accessibility for cellular processes. Desmin is a muscle-specific, cytoplasmic intermediate filament protein, the cytoplasmic roles of which are defined. Yet, there is some evidence pointing out nuclear functions for desmin. In silico and wet lab analysis shows that desmin can enter and function in the nucleus. Furthermore, the candidate nuclear partners of desmin support the notion that desmin can serve as a transcriptional regulator inside the nucleus. Uncovering the nuclear functions and partners of desmin will provide a new insight into the biological significance of desmin.