Abstract
Dynamin-2 (DNM2) is a large GTPase involved in clathrin-mediated endocytosis and related trafficking pathways. Mutations in human DNM2 cause two distinct neuromuscular disorders: centronuclear myopathy and Charcot-Marie-Tooth disease. Zebrafish have been shown to be an excellent animal model for many neurologic disorders, and this system has the potential to inform our understanding of DNM2-related disease. Currently, little is known about the endogenous zebrafish orthologs to human DNM2. In this study, we characterize two zebrafish dynamin-2 genes, dnm2 and dnm2-like. Both orthologs are structurally similar to human DNM2 at the gene and protein levels. They are expressed throughout early development and in all adult tissues examined. Knockdown of dnm2 and dnm2-like gene products resulted in extensive morphological abnormalities during development, and expression of human DNM2 RNA rescued these phenotypes. Our findings suggest that dnm2 and dnm2-like are orthologs to human DNM2, and that they are required for normal zebrafish development.
Highlights
Dynamins are large GTPases involved in a wide range of cell and organelle fission events
Using public databases (NCBI, ENSEMBL, ZFIN) and RACEPCR, we identified two separate zebrafish genes, dnm2 and dnm2like, which are highly related to human DNM2, on chromosomes 3 and 1 (Figure 1A; Genbank ID559334 and ID 406525; zfin zgc:114072 and zgc:77233)
Comparison of the two putative zebrafish genes with human dynamins revealed that both dnm2 and dnm2-like share highest sequence homology with human DNM2 (Figure 1C)
Summary
Dynamins are large GTPases involved in a wide range of cell and organelle fission events. Classical dynamins are critical components of clathrin-mediated endocytosis, where they contribute to the release of newly formed endosomes [1,2,3]. In addition to this well-characterized role in endocytosis, classical dynamins participate in a variety of membrane trafficking functions including phagocytosis, caveolae internalization, and trans-Golgi transport [4,5,6]. There are three classical dynamins: dynamin-1 (DNM1), dynamin (DNM2), and dynamin-3 (DNM3) Of these three genetic isoforms, only DNM2 is ubiquitously expressed [7,8,9] and a requirement for DNM2 during development is evidenced by an embryonic lethal phenotype in Dnm knockout mice [10]. Mutations in human DNM2 cause two different neuromuscular disorders; Charcot-Marie-Tooth disease and centronuclear myopathy [11,12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
