Dystrobrevin is required postsynaptically for homeostatic potentiation at the Drosophila NMJ

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1865

Article

Jantrapirom, Salinee^1,6  Nimlamool, Wutigri^1,2  Temviriyanukul, Piya³  Ahmadian, Somaieh⁴  Locke, Cody J.⁵  Davis, Graeme W.⁵  Yamaguchi, Masamitsu⁶  Noordermeer, Jasprina N.⁴  Fradkin, Lee G.^4,7  Potikanond, Saranyapin^1,2,4 

[1] Chiang Mai Univ, Fac Med, Dept Pharmacol, Chiang Mai, Thailand

[2] Chiang Mai Univ, Res Ctr Pharmaceut Nanotechnol, Chiang Mai, Thailand

[3] Mahidol Univ, Inst Nutr, Bangkok, Thailand

[4] Leiden Univ, Med Ctr, Dept Mol Cell Biol, Lab Dev Neurobiol, Leiden, Netherlands

[5] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA

[6] Kyoto Inst Technol, Dept Appl Biol, Sakyo Ku, Kyoto, Japan

[7] Univ Massachusetts, Med Sch, Amherst, MA 01003 USA

关键词: Dystrobrevin;    Dystrophin;    cdc42;    Neuromuscular junction;    Synaptic homeostasis;    Drosophila;   

DOI  :  10.1016/j.bbadis.2019.03.008

来源: Elsevier

【 摘 要 】

Evolutionarily conserved homeostatic systems have been shown to modulate synaptic efficiency at the neuromuscular junctions of organisms. While advances have been made in identifying molecules that function pre synaptically during homeostasis, limited information is currently available on how postsynaptic alterations affect presynaptic function. We previously identified a role for postsynaptic Dystrophin in the maintenance of evoked neurotransmitter release. We herein demonstrated that Dystrobrevin, a member of the Dystrophin Glycoprotein Complex, was delocalized from the postsynaptic region in the absence of Dystrophin. A newly generated Dystrobrevin mutant showed elevated evoked neurotransmitter release, increased bouton numbers, and a readily releasable pool of synaptic vesicles without changes in the function or numbers of postsynaptic glutamate receptors. In addition, we provide evidence to show that the highly conserved Cdc42 Rho GTPase plays a key role in the postsynaptic Dystrophin/Dystrobrevin pathway for synaptic homeostasis. The present results give novel insights into the synaptic deficits underlying Duchenne Muscular Dystrophy affected by a dysfunctional Dystrophin Glycoprotein complex.

【 授权许可】

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