| First Author | Ramakrishna S | Year | 2024 |
| Journal | Life Sci Alliance | Volume | 7 |
| Issue | 8 | PubMed ID | 38749544 |
| Mgi Jnum | J:348390 | Mgi Id | MGI:7640818 |
| Doi | 10.26508/lsa.202402594 | Citation | Ramakrishna S, et al. (2024) Distinct calcium sources regulate temporal profiles of NMDAR and mGluR-mediated protein synthesis. Life Sci Alliance 7(8) |
| abstractText | Calcium signaling is integral for neuronal activity and synaptic plasticity. We demonstrate that the calcium response generated by different sources modulates neuronal activity-mediated protein synthesis, another process essential for synaptic plasticity. Stimulation of NMDARs generates a protein synthesis response involving three phases-increased translation inhibition, followed by a decrease in translation inhibition, and increased translation activation. We show that these phases are linked to NMDAR-mediated calcium response. Calcium influx through NMDARs elicits increased translation inhibition, which is necessary for the successive phases. Calcium through L-VGCCs acts as a switch from translation inhibition to the activation phase. NMDAR-mediated translation activation requires the contribution of L-VGCCs, RyRs, and SOCE. Furthermore, we show that IP3-mediated calcium release and SOCE are essential for mGluR-mediated translation up-regulation. Finally, we signify the relevance of our findings in the context of Alzheimer's disease. Using neurons derived from human fAD iPSCs and transgenic AD mice, we demonstrate the dysregulation of NMDAR-mediated calcium and translation response. Our study highlights the complex interplay between calcium signaling and protein synthesis, and its implications in neurodegeneration. |
