Beclin 1 regulates astrocyte phagocytosis and phagosomal recruitment of retromer

Beclin 1 regulates astrocyte phagocytosis and phagosomal recruitment of retromer

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...

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Bibliographic Details
Published in:Tissue & cell Vol. 82; p. 102100
Main Authors: Lemus Silva, Evelyn G., Delgadillo, Yuberki, White, Robin E., Lucin, Kurt M.
Format: Journal Article
Language:English
Published: Scotland Elsevier Ltd 01-06-2023
Subjects:
Alzheimer Disease
Amyloid beta-Peptides - metabolism
Astrocytes
Astrocytes - metabolism
Beclin 1
Beclin-1 - metabolism
Humans
Phagocytosis
Phagocytosis - physiology
Retromer
SR-B1
Aβ
SR-BI
AD
PI3P
PI3K
Astrocytes
Beclin 1
3-MA
LV
SR-B1
Phagocytosis
Retromer
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Summary: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. •Reducing beclin 1 in astrocytes impairs the phagocytosis of latex beads and Aβ.•Reduced beclin 1 disrupts the function of the PI3-kinase Vps34.•Reduced beclin 1 impairs the recruitment of retromer to the phagosome.•Reduced beclin 1 diminishes the expression of the phagocytic receptor SR-BI.
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ISSN:0040-8166
1532-3072
DOI:10.1016/j.tice.2023.102100