4.7 Article

Exposure of a specific pleioform of multifunctional glyceraldehyde 3-phosphate dehydrogenase initiates CD14-dependent clearance of apoptotic cells

Journal

CELL DEATH & DISEASE
Volume 12, Issue 10, Pages -

Publisher

SPRINGERNATURE
DOI: 10.1038/s41419-021-04168-8

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Funding

  1. University Grants Commission India
  2. Indian Council of Medical Research
  3. CSIR
  4. DBT
  5. SERB DST
  6. Department of Biotechnology, India

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The study identified a specific form of GAPDH on the surface of apoptotic cells that interacts with CD14 on phagocytes, leading to engulfment. This novel interaction between multifunctional GAPDH and the phagocytic receptor CD14 results in apoptotic cell clearance, demonstrating a new mechanism for efferocytosis.
Rapid clearance of apoptotic cells by phagocytes is crucial for organogenesis, tissue homeostasis, and resolution of inflammation. This process is initiated by surface exposure of various 'eat me' ligands. Though phosphatidylserine (PS) is the best recognized general recognition ligand till date, recent studies have shown that PS by itself is not sufficient for clearance of apoptotic cells. In this study, we have identified a specific pleioform of GAPDH (Glyceraldehyde 3-phosphate dehydrogenase) that functions as an 'eat me' signal on apoptotic cell surface. This specific form of GAPDH which is exposed on surface of apoptotic cells was found to interact with CD14 present on plasma membrane of phagocytes leading to their engulfment. This is the first study demonstrating the novel interaction between multifunctional GAPDH and the phagocytic receptor CD14 resulting in apoptotic cell clearance (efferocytosis).

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