Caspase-3 Cleavage of Dishevelled Induces Elimination of Postsynaptic Structures
Autor: | Jin-Yuan Wang, Fei Chen, Xiu-Qing Fu, Chuang-Shi Ding, Li Zhou, Xiaohui Zhang, Zhen-Ge Luo |
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Rok vydání: | 2014 |
Předmět: |
chemistry.chemical_classification
animal structures Agrin Cell Biology Biology Neurotransmission General Biochemistry Genetics and Molecular Biology Neuromuscular junction Dishevelled Cell biology medicine.anatomical_structure chemistry Postsynaptic potential Synaptic plasticity medicine Cholinergic Molecular Biology Developmental Biology Acetylcholine receptor |
Zdroj: | Developmental Cell. 28:670-684 |
ISSN: | 1534-5807 |
Popis: | SummaryDuring the development of vertebrate neuromuscular junction (NMJ), agrin stabilizes, whereas acetylcholine (ACh) destabilizes AChR clusters, leading to the refinement of synaptic connections. The intracellular mechanism underlying this counteractive interaction remains elusive. Here, we show that caspase-3, the effector protease involved in apoptosis, mediates elimination of AChR clusters. We found that caspase-3 was activated by cholinergic stimulation of cultured muscle cells without inducing cell apoptosis and that this activation was prevented by agrin. Interestingly, inhibition of caspase-3 attenuated ACh agonist-induced dispersion of AChR clusters. Furthermore, we identified Dishevelled1 (Dvl1), a Wnt signaling protein involved in AChR clustering, as the substrate of caspase-3. Blocking Dvl1 cleavage prevented induced dispersion of AChR clusters. Finally, inhibition or genetic ablation of caspase-3 or expression of a caspase-3-resistant form of Dvl1 caused stabilization of aneural AChR clusters. Thus, caspase-3 plays an important role in the elimination of postsynaptic structures during the development of NMJs. |
Databáze: | OpenAIRE |
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