Focal cholesterol depletion during Fcγ receptor-mediated phagocytosis contributes to Lyn kinase regulation

Cholesterol-rich nanodomains, historically referred to as lipid rafts, have previously been reported to be critical for proper Fcγ Receptor and Lyn kinase signaling during phagocytosis. Throughout the initial stages of phagocytosis, the nascent phagosome is actively remodeled by localized lipid metabolism and exocytosis. However, to date, little is known about the dynamics of cholesterol during this stage of particle engulfment. Using a genetically-encoded biosensor for cholesterol, we find that cholesterol is depleted from the nascent phagosome prior to sealing. Additionally, protein markers of both cholesterol-rich and cholesterol-poor nanodomains also clear from the site of phagocytosis arguing against the selective depletion of specific membrane domains. Consistent with previous studies we find that exocytosis contributes to the remodeling of the nascent phagosome. The displacement of cholesterol from the forming phagosome was paralleled by Lyn kinase helping to explain the reduction of phosphotyrosine signal in the nascent phagosome. This diminution of cholesterol and Lyn from the base of the cup may aid in the processivity of the phagocytic signal during pseudopod extension, and provide an unappreciated mechanism by which Lyn kinase signaling is regulated during phagocytosis. Summary Statement: Localized exocytosis dilutes cholesterol from the phagocytic cup leading to the displacement of Lyn kinase and an attenuation of signaling.

• Publication year

  2018

• Venue

  bioRxiv

• Publication date

  2018-08-09

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1101/388637
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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