The Roles of the Numb Protein in Synaptic Development and Plasticity.

Numb is an adaptor protein with functions that include the endocytic processing of activated growth factor receptors. As growth factor signaling contributes to the development and function of the Drosophila neuromuscular junction (NMJ), we examined whether Numb is present at the larval NMJ and whether it is required for the growth, physiology, and/or plasticity of this synapse. Antisera prepared against Numb protein labeled NMJ presynaptic boutons, and RNAi knockdown of Numb, when directed to the presynaptic side, reduced the size of the NMJ. This was accompanied by smaller excitatory junctional potentials with reduced synaptic quantal content. Numb loss of function also suppressed the activity-dependent expansion of the NMJ, suggesting a requirement for Numb in synaptic growth plasticity. Similar phenotypes have been described at the NMJ for mutations of the Type II BMP growth factor receptor gene wishful thinking (wit). As Numb is known to participate in growth factor receptor signaling in other systems, we tested whether a genetic interaction exists between the numb and wit genes. We observed a reduction of NMJ size in double heterozygotes compared to the single heterozygote control, suggesting that Numb is a candidate for processing growth factor signals during synaptic development and plasticity at the larval NMJ.