Vps54 regulates Drosophila neuromuscular junction development and interacts genetically with Rab7 to control composition of the postsynaptic density
| Autor: | J. Todd Blankenship, Scott A. Barbee, Malea R. McGimsey, Emily L. Starke, Prajal H. Patel, Emily C. Wilkinson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
QH301-705.5
Science Protein subunit Neurodevelopment Neuromuscular Junction Vesicular Transport Proteins Syntaxin 16 Biology General Biochemistry Genetics and Molecular Biology Neuromuscular junction 03 medical and health sciences Vps54 0302 clinical medicine GARP Rab7 medicine Animals Drosophila Proteins Biology (General) Axon 030304 developmental biology Motor Neurons 0303 health sciences Gene knockdown Muscles Neurodegeneration fungi Post-Synaptic Density rab7 GTP-Binding Proteins GARP complex Epistasis Genetic Motor neuron medicine.disease Axons Cell biology medicine.anatomical_structure Drosophila melanogaster rab GTP-Binding Proteins Larva Drosophila Mutant Proteins General Agricultural and Biological Sciences Postsynaptic density Neuroglia 030217 neurology & neurosurgery Research Article trans-Golgi Network |
| Zdroj: | Biology Open article-version (VoR) Version of Record Biology Open, Vol 9, Iss 8 (2020) |
| ISSN: | 2046-6390 |
| Popis: | Vps54 is a subunit of the Golgi-associated retrograde protein (GARP) complex, which is involved in tethering endosome-derived vesicles to the trans-Golgi network (TGN). In the wobbler mouse, a model for human motor neuron (MN) disease, reduction in the levels of Vps54 causes neurodegeneration. However, it is unclear how disruption of the GARP complex leads to MN dysfunction. To better understand the role of Vps54 in MNs, we have disrupted expression of the Vps54 ortholog in Drosophila and examined the impact on the larval neuromuscular junction (NMJ). Surprisingly, we show that both null mutants and MN-specific knockdown of Vps54 leads to NMJ overgrowth. Reduction of Vps54 partially disrupts localization of the t-SNARE, Syntaxin-16, to the TGN but has no visible impact on endosomal pools. MN-specific knockdown of Vps54 in MNs combined with overexpression of the small GTPases Rab5, Rab7, or Rab11 suppresses the Vps54 NMJ phenotype. Conversely, knockdown of Vps54 combined with overexpression of dominant negative Rab7 causes NMJ and behavioral abnormalities including a decrease in postsynaptic Dlg and GluRIIB levels without any effect on GluRIIA. Taken together, these data suggest that Vps54 controls larval MN axon development and postsynaptic density composition through a mechanism that requires Rab7. Summary: The retrograde vesicle tethering factor, Vps54, regulates development of the Drosophila larval NMJ. Moreover, presynaptic Vps54 interacts genetically with the small GTPase, Rab7, to control NMJ growth and postsynaptic density composition. |
| Databáze: | OpenAIRE |
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