Redox regulation of CD21 shedding involves signaling via PKC and indicated the formation of a juxtamembrane stalk

Annette Aichem, Madhan Masilamani, Harald Illges

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Soluble CD21 (sCD21), released from the plasma membrane by proteolytic cleavage (shedding) of its extracellular domain (ectodomain) blocks B cell/follicular dendritic cell interaction and activates monocytes. We show here that both serine- and metalloproteases are involved in CD21 shedding. Using the oxidant pervanadate to mimic B cell receptor activation and thiol antioxidants such as N-acetylcysteine (NAC) and glutathione (GSH) we show that CD21 shedding is a redox-regulated process inducible by oxidation presumably through activation of a tyrosine kinase-mediated signal pathway involving protein kinase C (PKC), and by reducing agents that either directly activate the metalloprotease and/or modify intramolecular disulfide bridges within CD21 and thereby facilitate access to the cleavage site. Lack of short consensus repeat 16 (SCR16) abolishes CD21 shedding, and opening of the disulfide bridge between cys-2 (Cys941) and cys-4 (Cys968) of SCR16 is a prerequisite for CD21 shedding. Replacing these cysteines with selenocysteines (thereby changing the redox potential from -180 to -381 mV) results in a loss of inducible CD21 shedding, and removing this bridge by exchanging these cysteines with methionines increases CD21 shedding.

Original languageEnglish
Pages (from-to)2892-2902
Number of pages11
JournalJournal of Cell Science
Volume119
Issue number14
DOIs
StatePublished - 15 Jul 2006
Externally publishedYes

Keywords

  • B cells
  • CD21
  • Cell activation
  • Complement receptor
  • Diselenide bridge
  • Redox potential
  • Selenocysteine

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