Drosophila Exo70 Is Essential for Neurite Extension and Survival under Thermal Stress

The octomeric exocyst complex governs the final step of exocytosis in both plants and animals. Its roles, however, extend beyond exocytosis and include organelle biogenesis, ciliogenesis, cell migration, and cell growth. Exo70 is a conserved component of the exocyst whose function in is unclear. In...

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Veröffentlicht in:The Journal of neuroscience 2018-09, Vol.38 (37), p.8071-8086
Hauptverfasser: Koon, Alex Chun, Chen, Zhefan Stephen, Peng, Shaohong, Fung, Joyce Man See, Zhang, Xiaoman, Lembke, Kayly M, Chow, Hoi Kin, Frank, C Andrew, Jiang, Liwen, Lau, Kwok-Fai, Chan, Ho Yin Edwin
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Sprache:eng
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Zusammenfassung:The octomeric exocyst complex governs the final step of exocytosis in both plants and animals. Its roles, however, extend beyond exocytosis and include organelle biogenesis, ciliogenesis, cell migration, and cell growth. Exo70 is a conserved component of the exocyst whose function in is unclear. In this study, we characterized two mutant alleles of mutants exhibit reduced synaptic growth, locomotor activity, glutamate receptor density, and mEPSP amplitude. We found that presynaptic Exo70 is necessary for normal synaptic growth at the neuromuscular junction (NMJ). At the neuromuscular junction, genetically interacts with the small GTPase to regulate synaptic growth. Loss of Exo70 leads to the blockage of JNK signaling-, activity-, and temperature-induced synaptic outgrowths. We showed that this phenotype is associated with an impairment of integral membrane protein transport to the cell surface at synaptic terminals. In octopaminergic motor neurons, Exo70 is detected in synaptic varicosities, as well as the regions of membrane extensions in response to activity stimulation. Strikingly, mild thermal stress causes severe neurite outgrowth defects and pharate adult lethality in mutants. mutants also display defective locomotor activity in response to starvation stress. These results demonstrated that Exo70 is an important regulator of induced synaptic growth and is crucial for an organism's adaptation to environmental changes. The exocyst complex is a conserved protein complex directing secretory vesicles to the site of membrane fusion during exocytosis, which is essential for transporting proteins and membranes to the cell surface. Exo70 is a subunit of the exocyst complex whose roles in neurons remain elusive, and its function in is unclear. In , Exo70 is expressed in both glutamatergic and octopaminergic neurons, and presynaptic Exo70 regulates synaptic outgrowth. Moreover, mutants have impaired integral membrane transport to the cell surface at synaptic terminals and block several kinds of induced synaptic growth. Remarkably, elevated temperature causes severe arborization defects and lethality in mutants, thus underpinning the importance of Exo70 functions in development and adaptation to the environment.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.0620-18.2018