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Calpains are calcium-dependent, cytosolic proteinases active at neutral pH. They do not degrade but cleave substrates at limited sites. Calpains are implicated in various pathologies, such as ischemia, injuries, muscular dystrophy, and neurodegeneration. Despite so, the physiological function of calpains remains to be clearly defined. Using the neuromuscular junction of Drosophila of both sexes as a model, we performed RNAi screening and uncovered that calpains negatively regulated protein levels of the glutamate receptor GluRIIA but not GluRIIB. We then showed that calpains enrich at the postsynaptic area, and the calcium-dependent activation of calpains induced cleavage of GluRIIA at Q788 of its C terminus. Further genetic and biochemical experiments revealed that different calpains genetically and physically interact to form a protein complex. The protein complex was required for the proteinase activation to downregulate GluRIIA. Our data provide a novel insight into the mechanisms by which different calpains act together as a complex to specifically control GluRIIA levels and consequently synaptic function.SIGNIFICANCE STATEMENT Calpain has been implicated in neural insults and neurodegeneration. However, the physiological function of calpains in the nervous system remains to be defined. Here, we show that calpain enriches at the postsynaptic area and negatively and specifically regulates GluRIIA, but not IIB, level during development. Calcium-dependent activation of calpain cleaves GluRIIA at Q788 of its C terminus. Different calpains constitute an active protease complex to cleave its target. This study reveals a critical role of calpains during development to specifically cleave GluRIIA at synapses and consequently regulate synaptic function.
Pubmed ID: 30705102 RIS Download
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This unknown targets Mouse IgG (H+L)
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View all literature mentionsThis polyclonal targets 6X His tag??
View all literature mentionsThis monoclonal targets HA
View all literature mentionsThis polyclonal targets CalpA
View all literature mentionsThis polyclonal targets GluRIIB
View all literature mentionsThis monoclonal targets Discs large (Drosophila)
View all literature mentionsThis monoclonal targets Glutamate receptor subunit, DGluR-IIA
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+m*]=Mhc.GluRIIB.Myc}3 from BDSC.
View all literature mentionsSoftware suite for electrophysiology data acquisition and analysis by Molecular Devices. Used for the control and recording of voltage clamp, current clamp, and patch clamp experiments. The software suite consists of Clampex 11 Software for data acquisition, AxoScope 11 Software for background recording, Clampfit 11 Software for data analysis, and optional Clampfit Advanced Analysis Module for sophisticated and streamlined analysis.
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View all literature mentionsImage processing software used to modify and clarify sample images for FluoView FV1000 range of confocal laser scanning microscopes and Fluoview FV1000MPE multiphoton excitation systems. The software incorporates high-dynamic-range imaging, minimized signal-to-noise ratios, partial stitching with multiarea time-lapse imaging, and channel unmixing. The software also allows users to select specific areas of the whole sample, which can stitched together.
View all literature mentionsSoftware for image capture, processing and analysis with Leica fluorescence and confocal microscopes.
View all literature mentionsCell line Schneider 2 is a Spontaneously immortalized cell line with a species of origin Drosophila melanogaster
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+m*]=Mhc.GluRIIA.Myc}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+m*]=Mhc.GluRIIB.Myc}3 from BDSC.
View all literature mentionsSoftware suite for electrophysiology data acquisition and analysis by Molecular Devices. Used for the control and recording of voltage clamp, current clamp, and patch clamp experiments. The software suite consists of Clampex 11 Software for data acquisition, AxoScope 11 Software for background recording, Clampfit 11 Software for data analysis, and optional Clampfit Advanced Analysis Module for sophisticated and streamlined analysis.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsThis unknown targets Mouse IgG (H+L)
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