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Nature. 1995 Sep 7;377(6544):75-9.

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

Author information

1
Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.

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.

PMID:
7544874
DOI:
10.1038/377075a0
[Indexed for MEDLINE]

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