Beclin 1 regulates astrocyte phagocytosis and phagosomal recruitment of retromer.

Evelyn G Lemus Silva, Yuberki Delgadillo, Robin E White, Kurt M Lucin

Tissue & cell 2023 Jun

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Phagocytosis plays an important role in maintaining brain homeostasis and when impaired can result in the accumulation of unwanted cellular material. While microglia are traditionally considered the phagocytes of the brain, astrocytes are also capable of phagocytosis and are the most numerous cells in the brain. In Alzheimer's disease (AD), astrocytes can be found surrounding β-amyloid (Aβ) plaques yet they seem unable to eliminate these deposits, suggesting phagocytosis may be impaired in AD. Mechanisms that might diminish astrocyte phagocytosis in AD are currently unclear. Here, we demonstrate that the autophagy protein beclin 1, which is reduced in AD, plays a role in regulating astrocyte phagocytosis. Specifically, we show that reducing beclin 1 in C6 astrocytes impairs the phagocytosis of latex beads, reduces retromer levels, and impairs retromer recruitment to the phagosomal membrane. Furthermore, we show that these beclin 1-mediated changes are accompanied by reduced expression of the phagocytic receptor Scavenger Receptor Class B type I (SR-BI). Collectively, these findings suggest a critical role for the protein beclin 1 in both receptor trafficking and receptor-mediated phagocytosis in astrocytes. Moreover, these findings provide insight into mechanisms by which astrocytes may become impaired in AD. Copyright © 2023 Elsevier Ltd. All rights reserved.

Citation

Evelyn G Lemus Silva, Yuberki Delgadillo, Robin E White, Kurt M Lucin. Beclin 1 regulates astrocyte phagocytosis and phagosomal recruitment of retromer. Tissue & cell. 2023 Jun;82:102100