Transient Receptor Potential ‘Melastatin’ 7 (TRPM7) is a ubiquitously expressed, non-selective divalent cation channel implicated in diverse cellular functions including actomyosin cytoskeletal remodeling, magnesium homeostasis, and anoxic neuronal death. The present study investigates the role of TRPM7 in modulating neuronal morphology and regulating neuronal cytoskeletal dynamics after anoxia. Overexpression of GFP-tagged TRPM7 in neuronal cultures caused a stunted morphology with fewer neurite branches than controls, suggesting that TRPM7 regulates the neuronal cytoskeleton during dendritic outgrowth. I have discovered that TRPM7 may regulate morphology via activation of cofilin-1 (an actin binding protein). I found that TRPM7-dependent cofilin activation during anoxia mediated neuronal death. Overall my work reveals a novel link between anoxia-induced TRPM7 activity and cofilin activation, which likely contributes to neurodegeneration after ischemia.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/30181 |
| Date | 01 December 2011 |
| Creators | Bent, Russell |
| Contributors | Aarts, Michelle |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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