Epidermal growth factor-like domain repeat of stabilin-2 recognizes phosphatidylserine during cell corpse clearance

Seung Yoon Park, So Youn Kim, Mi Yeon Jung, Dong Jun Bae, In-San Kim

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Exposure of phosphatidylserine (PS) on the cell surface occurs early during apoptosis and serves as a recognition signal for phagocytes. Clearance of apoptotic cells by a membrane PS receptor is one of the critical anti-inflammatory functions of macrophages. However, the PS binding receptors and their recognition mechanisms have not been fully investigated. Recently, we reported that stabilin-2 is a PS receptor that mediates the clearance of apoptotic cells, thus releasing the anti-inflammatory cytokine, transforming growth factor β. In this study, we showed that epidermal growth factor (EGF)-like domain repeats (EGFrp) in stabilin-2 can directly and specifically recognize PS. The EGFrps also competitively impaired apoptotic cell uptake by macrophages in in vivo models. We also showed that calcium ions are required for stabilin-2 to mediate phagocytosis via EGFrp. Interestingly, at least four tandem repeats of EGF-like domains were required to recognize PS, and the second atypical EGF-like domain in EGFrp was critical for calcium-dependent PS recognition. Considering that PS itself is an important target molecule for both apoptotic cells and nonapoptotic cells during various cellular processes, our results should help elucidate the molecular mechanism by which apoptotic cell clearance in the human body occurs and also have implications for targeting PS externalization of nonapoptotic cells.

Original languageEnglish
Pages (from-to)5288-5298
Number of pages11
JournalMolecular and Cellular Biology
Volume28
Issue number17
DOIs
Publication statusPublished - 2008 Sep 1
Externally publishedYes

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Phosphatidylserines
Cadaver
Epidermal Growth Factor
Anti-Inflammatory Agents
Macrophages
Calcium
Tandem Repeat Sequences
Transforming Growth Factors
Phagocytes
Human Body
Phagocytosis
Cell Membrane
Ions
Apoptosis
Cytokines
phosphatidylserine receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Epidermal growth factor-like domain repeat of stabilin-2 recognizes phosphatidylserine during cell corpse clearance. / Park, Seung Yoon; Kim, So Youn; Jung, Mi Yeon; Bae, Dong Jun; Kim, In-San.

In: Molecular and Cellular Biology, Vol. 28, No. 17, 01.09.2008, p. 5288-5298.

Research output: Contribution to journalArticle

Park, Seung Yoon ; Kim, So Youn ; Jung, Mi Yeon ; Bae, Dong Jun ; Kim, In-San. / Epidermal growth factor-like domain repeat of stabilin-2 recognizes phosphatidylserine during cell corpse clearance. In: Molecular and Cellular Biology. 2008 ; Vol. 28, No. 17. pp. 5288-5298.
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