Aproteoglycan helps disperse Wnt proteins during development of the neuromuscular junction, Kamimura et al. reveal.
Wnt proteins help shape many parts of a developing embryo, including neuromuscular junctions where nerves connect to muscles. In fruit flies, the Wnt protein Wingless (Wg) stimulates the presynaptic side of the junction, spurring the growth of synaptic boutons. Wg also prompts differentiation of the postsynaptic side of the junction. However, researchers don’t know how the hydrophobic Wg is parceled out to the presynaptic and postsynaptic membranes. One possible mechanism involves heparan sulfate proteoglycans, which latch onto Wg and help set up concentration gradients of the protein.
To determine whether proteoglycans help distribute Wg, Kamimura et al. scrutinized fly larvae with mutated versions of Trol, a gene that codes for the proteoglycan perlecan. The insects showed defects on both sides of their neuromuscular junctions. Wg built up on the presynaptic side, which sprouted extra boutons. Postsynaptic flaws included puny muscles and an undersized subsynaptic reticulum (SSR), a highly folded region on the muscle membrane. Stimulating the nerve provoked a weak current, indicating that the neuromuscular junctions in the mutants malfunctioned.
Trol normally gathers at the SSR, the researchers found. Whether Trol helps transport Wg across the synapse isn’t clear, but it ensures that an ample supply of Wg reaches the postsynaptic side. Without Trol, excess Wg accumulates on the presynaptic side and triggers the growth of extraneous synaptic boutons.
Text by Mitch Leslie