Figure 9.

Multiple elements of the PLD1 pathway modify ALS-related phenotypes. Shown is a schematic depicting biochemical relationships leading to Pld production (Foster and Xu 2003). Red arrows point to pathway components identified as modifiers in our GMR-hFUS^R521C and/or GMR-hTDP-43^M337V screens. Green arrows point to elements reported to be upregulated in patients with early-onset, but not late-onset, ALS. In both the primary and validation screens six different Drosophila orthologs of components of the PLD1 pathway were recovered as modifiers of GMR-hFUS^R521C and GMR-hTDP-43^M337V: dPld, ArfGAP3, Rgl, Ras85D, Plc21C, and Rho1, which correspond to the human genes, PLD1, ARFGAP3, RALGDS, KRAS, PLCB1, and RHOA.