Ca2+- and calcineurin-dependent recycling of an integrin to the front of migrating neutrophils Academic Article uri icon

Overview

MeSH Major

  • Calcium
  • Calmodulin-Binding Proteins
  • Integrins
  • Neutrophils
  • Phosphoprotein Phosphatases
  • Receptors, Vitronectin

abstract

  • 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 date

  • September 7, 1995

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 7544874

Additional Document Info

start page

  • 75

end page

  • 9

volume

  • 377

number

  • 6544