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Atypical Cadherin FAT3 Is a Novel Mediator for Morphological Changes of Microglia

岡島, 智美 筑波大学

2021.08.17

概要

Microglia are resident macrophages, which are critical for brain development and homeostasis. Microglial morphology is dynamically changed during postnatal stages, leading to regulating neural circuit formation, including neurogenesis, synaptogenesis, and synapse pruning. The functional transition in microglia has been considered to correlate with their morphological changes over time. In previous research, it has been well known that the shape of microglia is also altered in response to the detritus of the apoptotic cells and pathogens such as bacteria and viruses. Although the morphological changes are crucial for acquiring microglial functions, the morphological changes of microglia during juvenile rather than adults are not fully understood. Here I report that an atypical cadherin family protein, FAT3, regulates microglial morphology by contributing to the stabilization of microglial projections. I found that the shape of mouse microglia cell line BV2 becomes elongated in a high nutrient medium. Using microarray analysis, I identified that FAT3 expression is induced by culturing at high nutrient medium. Knockdown of FAT3 increased the number of round shapes and shortens the time of sustaining the elongation forms. Moreover, I found that purinergic analog, hypoxanthine, promotes FAT3 expression and morphological changes in BV2. Additionally, the microglial ramifications and synapse pruning are enhanced in FAT3 deficient mice. These data suggest that the FAT3 expression associated with hypoxanthine is a novel pathway associated with microglial morphology and functions. My data provide a possibility that microglial FAT3 control brain homeostasis via regulation of microglial morphology and functions in vivo.

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