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. Author manuscript; available in PMC: 2015 Dec 1.
Published in final edited form as: Nat Med. 2015 May 11;21(6):601–609. doi: 10.1038/nm.3843

Figure 1.

Figure 1

Dynamin oligomerization is essential for kidney function. (a) Phenotype of zebrafish larvae injected with either scrambled (Control MO) or dynamin-2-specific morpholino (dnm2 MO) 120 hours post-fertilization. Scale bars, 2 mm. (b) Survivorship curves of zebrafish larvae injected with either Control MO or dnm2 MO. Each curve represents 180 animals for Control MO and 245 animals for dnm2 MO. Error bars, mean ± SD (log-rank: P < 0.0001 for comparison of mean survival time). (c) Representative image of the fluorescence of circulating eGFP-DBP in the retinal vessel plexus of the fish eye 96 hours post-fertilization and injected with either control MO or dnm2 MO (left) (n = 128 images for control MO, and n = 94 images for dnm2 MO animals). Scale bars, 100 μm. Transmission electron micrographs of glomeruli analyzed in zebrafish larvae 120 hours post-fertilization and injected with either control MO or dnm2 MO (right). Scale bars, 0.5 μm. (d) Intensity of circulating eGFP-DBP (AU, arbitrary units) in the retinal vessel plexus of the fish eye 96 hours post-fertilization and treated with the indicated MO and/or expression construct and with Bis-T-23 (1 ng per larvae) or with DMSO as vehicle (20% per larvae). For groups 1–6, 16, and 20, n = 100–150; for all other groups n = 40–100. Black lines represent median intensity in each group (**P ≤ 0.01, ***P ≤ 0.001, unpaired t-test). (e) A schematic diagram indicating the domain structures of dynamin: GTPase, Middle, PH (Pleckstrin-Homology), GED (GTPase Effector Domain), and PRD (Proline/arginine-Rich Domain). Indicated mutations: K/E (K-to-E mutations of the indicated amino acid residues in black), E/K (E-to-K mutations of the indicated residues in red) and I690K. (f) A schematic diagram indicating that dimers of dynamin (DynDIMER) and tetramers of dynamin (DynTETRA) exhibit basal rate of GTP hydrolysis. Oligomerized dynamin (DynOLIGO), whose formation is promoted by Bis-T-23 (structure shown at right) or through indicated mutations, exhibits increased rate of GTP hydrolysis. DynOLIGO induces actin polymerization and crosslinking of F-actin, which in turn regulates the structure and function of podocytes. The small arrows in e and f indicate the effect of the mutations on dynamin’s propensity to oligomerize.