MassIVE MSV000090254

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Polarized microtubule remodeling transforms activated microglia morphology and drives cytokine release

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Description

Microglial activation is a pathological hallmark in many neurodegenerative diseases. During activation, microglia undergo complex morphological changes, including loss of their characteristic ramified cell morphology, which is routinely used to detect and quantify inflammation in the brain. However, the molecular mechanisms enabling this morphological change and the relation between microglial cell morphology and its pathophysiological function are not understood. Here, proteomic profiling of activated microglia identified microtubule remodeling pathways as an early factor that drives the morphological change and subsequently controls cytokine responses. We found that activated microglia increase their microtubule dynamics to form a stable and centrosomally anchored microtubule array to facilitate efficient cytokine trafficking and release. Moreover, we identified cyclin-dependent kinase 1 (Cdk-1) as a critical upstream regulator of microtubule remodeling and morphological change in vitro and in vivo. These results demonstrate a critical role for microtubule dynamics and reorganization in microglial activation and modulating cytokine-mediated inflammatory responses. [doi:10.25345/C5TT4FZ0P] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Microglia ; TMT ; TMTpro ; LPS ; Proteome

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Principal Investigators:
(in alphabetical order) 		Christopher Rose, Genentech, United States
Submitting User: CMRose5
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