bfc, a novel serpent co-factor for the expression of croquemort, regulates efferocytosis in Drosophila melanogaster

PLoS Genet. 2021 Dec 3;17(12):e1009947. doi: 10.1371/journal.pgen.1009947. eCollection 2021 Dec.

Abstract

Efferocytosis is the process by which phagocytes recognize, engulf, and digest (or clear) apoptotic cells during development. Impaired efferocytosis is associated with developmental defects and autoimmune diseases. In Drosophila melanogaster, recognition of apoptotic cells requires phagocyte surface receptors, including the scavenger receptor CD36-related protein, Croquemort (Crq, encoded by crq). In fact, Crq expression is upregulated in the presence of apoptotic cells, as well as in response to excessive apoptosis. Here, we identified a novel gene bfc (booster for croquemort), which plays a role in efferocytosis, specifically the regulation of the crq expression. We found that Bfc protein interacts with the zinc finger domain of the GATA transcription factor Serpent (Srp), to enhance its direct binding to the crq promoter; thus, they function together in regulating crq expression and efferocytosis. Overall, we show that Bfc serves as a Srp co-factor to upregulate the transcription of the crq encoded receptor, and consequently boosts macrophage efferocytosis in response to excessive apoptosis. Therefore, this study clarifies how phagocytes integrate apoptotic cell signals to mediate efferocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • CD36 Antigens / genetics
  • Drosophila Proteins* / genetics
  • Drosophila melanogaster / genetics
  • GATA Transcription Factors* / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Macrophages / metabolism
  • Phagocytes* / metabolism
  • Phagocytosis* / genetics
  • Receptors, Cell Surface / genetics
  • Receptors, Scavenger* / genetics

Substances

  • CD36 Antigens
  • crq protein, Drosophila
  • Drosophila Proteins
  • GATA Transcription Factors
  • Receptors, Cell Surface
  • Receptors, Scavenger
  • srp protein, Drosophila
  • bfc protein, Drosophila

Grants and funding

H.X. received grants 91954114 and 31671439 from the National Natural Science Foundation of China (http://www.nsfc.gov.cn).Q.Z. received grant 31801164 from the National Natural Science Foundation of China (http://www.nsfc.gov.cn). H.X. received grants GK202001004 and GK202007009 from Shaanxi Normal University (http://www.snnu.edu.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.