Publications
Product
| 지원과제 | cPMTb |
| 저자명 | Nhung TTM, Long NP, Nghi TD, Suh YJ, Anh NH, Jung CW, Triet HM, Jung MK, Woo YS, Yoo JY, Noh SJ, Kim SJ, Lee SB, Park SO, Thomas G, Simmen T, Mun JY, Rhee RW, Kwon SW, Park SK |
| 학회정보 | Proc Natl Acad Sci U S A. 8;120(32):e2303402120 / 2023.08 |
| 제 목 | Genome-wide kinase-MAM interactome screening reveals the role of CK2A1 in MAM Ca2+ dynamics linked to DEE66 |
| LINK | www.ncbi.nlm.nih.gov/pubmed/37523531/ |
| 게시일 | 2025-03-31 11:41:40 |
| 년도 | |
| 내용 | The endoplasmic reticulum (ER) and mitochondria form a unique subcellular compartment called mitochondria-associated ER membranes (MAMs). Disruption of MAMs impairs Ca2+ homeostasis, triggering pleiotropic effects in the neuronal system. Genome-wide kinase-MAM interactome screening identifies casein kinase 2 alpha 1 (CK2A1) as a regulator of composition and Ca2+ transport of MAMs. CK2A1-mediated phosphorylation of PACS2 at Ser207/208/213 facilitates MAM localization of the CK2A1-PACS2-PKD2 complex, regulating PKD2-dependent mitochondrial Ca2+ influx. We further reveal that mutations of PACS2 (E209K and E211K) associated with developmental and epileptic encephalopathy-66 (DEE66) impair MAM integrity through the disturbance of PACS2 phosphorylation at Ser207/208/213. This, in turn, causes the reduction of mitochondrial Ca2+ uptake and the dramatic increase of the cytosolic Ca2+ level, thereby, inducing neurotransmitter release at the axon boutons of glutamatergic neurons. In conclusion, our findings suggest a molecular mechanism that MAM alterations induced by pathological PACS2 mutations modulate Ca2+-dependent neurotransmitter release.
Keywords: calcium; casein kinase 2; developmental and epileptic encephalopathy-66; mitochondria-associated ER membranes. |
