Abnormal larval neuromuscular junction morphology and physiology in prickle isoform mutants with known axonal transport defects and adult seizure behavior.

Previous studies have demonstrated the striking mutational effects of the planar cell polarity gene on larval motor axon microtubule-mediated vesicular transport and on adult epileptic behavior associated with neuronal circuit hyperexcitability. Mutant alleles of the - () and - () isoforms (hereafter referred to as and alleles, respectively) exhibit differential phenotypes. While both and affect larval motor axon transport, only confers motor circuit and behavior hyperexcitability. However, mutations in the two isoforms apparently counteract to ameliorate adult motor circuit and behavioral hyperexcitability in heteroallelic flies. We have further investigated the consequences of altered axonal transport in the development and function of the larval neuromuscular junction (NMJ). We uncovered robust dominant phenotypes in both and alleles, including synaptic terminal overgrowth (as revealed by anti-HRP and -Dlg immunostaining) and poor vesicle release synchronicity (as indicated by synaptic bouton focal recording). However, we observed recessive alteration of synaptic transmission only in larvae, i.e. increased excitatory junctional potential (EJP) amplitude in but not in /+ or /. Interestingly, for motor terminal excitability sustained by presynaptic Ca channels, both and exerted strong effects to produce prolonged depolarization. Notably, only acted dominantly whereas /+ appeared normal, but was able to suppress the phenotypes, i.e. appeared normal. Our observations contrast the differential roles of the and isoforms and highlight their distinct, variable phenotypic expression in the various structural and functional aspects of the larval NMJ.