Ca(2+)- and calcineurin-dependent recycling of an integrin to the front of migrating neutrophils

Nature. 1995 Sep 7;377(6544):75-9. doi: 10.1038/377075a0.


Chemoattractants stimulate neutrophil migration by activating signalling pathways including repeated transient increases in intracellular free calcium, [Ca2+]i. A motile neutrophil sends out many pseudopods, some of which adhere to the substrate; to continue moving forward the cell must release these attachments. Adhesion can be actively regulated, and neutrophils in which [Ca2+]i transients are inhibited become stuck on fibronectin or vitronectin, extracellular matrix proteins that neutrophils encounter in vivo. Function-blocking antibodies to beta 3 integrins or the alpha v beta 3 heterodimer restore motility on vitronectin to [Ca2+]i-buffered cells (B. Hendey, M.A.L., E. Marcantonio and F.R.M., manuscript submitted), indicating that an alpha v beta 3-like integrin is responsible for the [Ca2+]i-sensitive adhesion. We show that the density of alpha v beta 3 integrins in the adherent membrane of neutrophils migrating on vitronectin is much higher at the leading edge than at the rear, but [Ca2+]i buffering or inhibition of Ca(2+)-calmodulin-activated protein phosphatase 2B (calcineurin) leads to accumulation of alpha v beta 3 on the adherent surface at the rear of the cell. We show that the polarized distribution of alpha v beta 3 integrins in migrating neutrophils is maintained by [Ca2+]i-dependent release of adhesion followed by endocytosis of these integrins and recycling to the leading edge.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcineurin
  • Calcium / metabolism*
  • Calmodulin-Binding Proteins / metabolism*
  • Cell Adhesion
  • Cell Membrane / metabolism
  • Chemotaxis, Leukocyte
  • Endocytosis
  • Extracellular Matrix Proteins / metabolism
  • Fluorescent Antibody Technique
  • Glycoproteins / metabolism
  • Humans
  • In Vitro Techniques
  • Integrins / metabolism*
  • Microscopy, Confocal
  • Neutrophils / metabolism*
  • Neutrophils / ultrastructure
  • Phosphoprotein Phosphatases / metabolism*
  • Pseudopodia / metabolism
  • Receptors, Vitronectin*
  • Talin / metabolism
  • Vitronectin


  • Calmodulin-Binding Proteins
  • Extracellular Matrix Proteins
  • Glycoproteins
  • Integrins
  • Receptors, Vitronectin
  • Talin
  • Vitronectin
  • integrin alphaVbeta5
  • Calcineurin
  • Phosphoprotein Phosphatases
  • Calcium