Figure 1.

Dynein organization and phenotypic analysis of Dhc disease-associated mutations in Drosophila. (A) Cartoon of human dynein complex with alternative nomenclature for subunits shown. The C-terminal domain of DYNC1H1 is not visible in this view because it lies on the other face of the AAA+ rings. (B) Positions in human DYNC1H1 of the disease-associated mutations characterized in this study. Domains of DYNC1H1 are color-coded as in panel A. Mouse Loa mutation is numbered according to the equivalent residue in human DYNC1H1. Adapted from Hoang et al. (2017). (C) Summary of in vitro and in vivo effects of disease-associated mutations. SV, synaptic vesicle. In vitro effects refer to when both copies of DYNC1H1 in the dynein complex contain the mutation; in vivo effects refer to the homozygous condition. (D) Images showing short bristles on the notum of homozygous F579Y adult flies compared to controls (yw). Arrowheads point to posterior scutellar macrochaetae as an example. The bristle phenotype of F579Y flies was completely penetrant (>160 flies examined). (E) Confocal images of segmental nerves (taken proximal to the ventral ganglion; anterior to top; Z-projections) from fixed L3 larvae stained for the synaptic vesicle proteins Synaptotagmin (Syt) and Cysteine-string protein (CSP). Arrowheads show examples of synaptic vesicle accumulations in a subset of mutant genotypes. Images are representative of three to six larvae analyzed per genotype. Scale bars: D, 500 µm; E, 50 µm.