1. The PDZ-GEF Gef26 regulates synapse development and function via FasII and Rap1 at the Drosophila neuromuscular junction
- Author
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Su Wang, Xiankun Zeng, Steven X. Hou, Huihui Lv, Wei Xie, Mingkuan Sun, Jinsong An, and Mengzhu Ou
- Subjects
0301 basic medicine ,animal structures ,Cell Adhesion Molecules, Neuronal ,PDZ domain ,Telomere-Binding Proteins ,Morphogenesis ,Neuromuscular Junction ,Presynaptic Terminals ,Small G Protein ,Biology ,Synaptic Transmission ,Article ,Shelterin Complex ,Synapse ,03 medical and health sciences ,0302 clinical medicine ,Cell Adhesion ,Animals ,Drosophila Proteins ,Guanine Nucleotide Exchange Factors ,Cell adhesion ,fungi ,Cell Biology ,Cell biology ,030104 developmental biology ,nervous system ,030220 oncology & carcinogenesis ,Larva ,Synapses ,Rap1 ,Drosophila ,Guanine nucleotide exchange factor ,Signal transduction ,Signal Transduction - Abstract
Guanine nucleotide exchange factors (GEFs) are essential for small G proteins to activate their downstream signaling pathways, which are involved in morphogenesis, cell adhesion, and migration. Mutants of Gef26, a PDZ-GEF (PDZ domain-containing guanine nucleotide exchange factor) in Drosophila, exhibit strong defects in wings, eyes, and the reproductive and nervous systems. However, the precise roles of Gef26 in development remain unclear. In the present study, we analyzed the role of Gef26 in synaptic development and function. We identified significant decreases in bouton number and branch length at larval neuromuscular junctions (NMJs) in Gef26 mutants, and these defects were fully rescued by restoring Gef26 expression, indicating that Gef26 plays an important role in NMJ morphogenesis. In addition to the observed defects in NMJ morphology, electro-physiological analyses revealed functional defects at NMJs, and locomotor deficiency appeared in Gef26 mutant larvae. Furthermore, Gef26 regulated NMJ morphogenesis by regulating the level of synaptic Fasciclin II (FasII), a well-studied cell adhesion molecule that functions in NMJ development and remodeling. Finally, our data demonstrate that Gef26-specific small G protein Rap1 worked downstream of Gef26 to regulate the level of FasII at NMJs, possibly through a βPS integrin-mediated signaling pathway. Taken together, our findings define a novel role of Gef26 in regulating NMJ development and function.
- Published
- 2018