Muscle associated Drosophila adducin regulates Drosophila larval neuromuscular junction (NMJ) development and the localization of Draper to the synapse. Mannan Wang1, Simon Wang2, Charles Krieger1, Nicholas Harden2, Wade Parkhouse1. 1) Department of Biomedical Physiology and Kinesiology, SFU, Burnaby, BC, Canada; 2) Department of Molecular Biology and Biochemistry, SFU, Burnaby, BC, Canada.
Adducin, the cross linker of actin and spectrin, has important regulatory roles in the remodeling of actin-spectrin cytoskeleton which permits modification of the membrane at sites of cell-cell contact during synaptic plasticity. Cell-cell contact is affected in neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) where loss of synaptic contact between motor neurons and muscle is associated with motor neuron degeneration. Adducin was found hyperphosphorylated in nervous system tissue in patients with ALS, suggesting its potential association with the etiology of ALS. In Drosophila, Drosophila adducins, encoded by hu-li tai shao (hts), are localized to both pre-synaptic and post-synaptic larval neuromuscular junction (NMJ). Here we specifically examined the effects of post-synaptic (muscle-associated) Hts manipulation on NMJ development. Results show that in animals with muscle-specific knock-down of Hts, NMJs are underdeveloped, whereas overexpression of Hts in the muscle results in NMJ overgrowth. Draper, a transmembrane engulfment receptor, has also been shown to regulate Drosophila larval NMJ development. Our results show that Draper is co-localized with Hts to the postsynaptic NMJ, suggesting potential interaction between Draper and Hts. Interestingly, we found that in animals with muscle-specific knock-down of Hts, the immunoreactivity of Draper was tighter localized to the synapse, whereas overexpression of Hts caused delocalization of Draper immunoreactivity from the synapse. The effects of muscle-associated Hts on the targeting of Draper to the synapse highlights a new avenue by which Hts may be exerting its influence on NMJ development and opens up worthwhile possibilities for future studies.