INF2-mediated actin filament reorganization confers intrinsic resilience to neuronal ischemic injury.

Autor: Calabrese B; Department of Neurobiology, School of Biological Sciences, University of California, San Diego, and Sanford Consortium for Regenerative Medicine, La Jolla, CA, 92093, USA., Jones SL; Department of Biology, University of Pennsylvania, Philadelphia, PA, 19104-4544, USA., Shiraishi-Yamaguchi Y; Japan Science and Technology Agency (JST), Tokyo, 102-8666, Japan., Lingelbach M; Neurosciences Interdepartmental Program, Stanford University, Stanford, CA, 94305, USA., Manor U; The Salk Institute for Biological Studies, La Jolla, CA, 92037, USA., Svitkina TM; Department of Biology, University of Pennsylvania, Philadelphia, PA, 19104-4544, USA., Higgs HN; Department of Biochemistry, Geisel School of Medicine, Hanover, NH, 03755, USA., Shih AY; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, 98101, USA.; Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA., Halpain S; Department of Neurobiology, School of Biological Sciences, University of California, San Diego, and Sanford Consortium for Regenerative Medicine, La Jolla, CA, 92093, USA. shalpain@ucsd.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Oct 13; Vol. 13 (1), pp. 6037. Date of Electronic Publication: 2022 Oct 13.
DOI: 10.1038/s41467-022-33268-y
Abstrakt: During early ischemic brain injury, glutamate receptor hyperactivation mediates neuronal death via osmotic cell swelling. Here we show that ischemia and excess NMDA receptor activation cause actin to rapidly and extensively reorganize within the somatodendritic compartment. Normally, F-actin is concentrated within dendritic spines. However, <5 min after bath-applied NMDA, F-actin depolymerizes within spines and polymerizes into stable filaments within the dendrite shaft and soma. A similar actinification occurs after experimental ischemia in culture, and photothrombotic stroke in mouse. Following transient NMDA incubation, actinification spontaneously reverses. Na + , Cl - , water, and Ca 2+ influx, and spine F-actin depolymerization are all necessary, but not individually sufficient, for actinification, but combined they induce activation of the F-actin polymerization factor inverted formin-2 (INF2). Silencing of INF2 renders neurons vulnerable to cell death and INF2 overexpression is protective. Ischemia-induced dendritic actin reorganization is therefore an intrinsic pro-survival response that protects neurons from death induced by cell edema.
(© 2022. The Author(s).)
Databáze: MEDLINE
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