Dynamin function is important for CC-chemokine receptor induced cell migration

Jacques, Richard O., Mills, Shirley C., Cazzonatto Zerwes, Paula, Fagade, Feyisope O., Green, John E., Downham, Scott, Sexton, Darren W. and Mueller, Anja (2015) Dynamin function is important for CC-chemokine receptor induced cell migration. Cell Biochemistry and Function, 33 (6). pp. 407-414. ISSN 0263-6484

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Abstract

The HIV viral entry co-receptors CCR5 and CXCR4 function physiologically as typical chemokine receptors. Activation leads to cytosolic signal transduction that results in a variety of cellular responses such as cytoskeletal rearrangement and chemotaxis (CTX). Our aim was to investigate the signalling pathways involved in CC-and CXC-receptor mediated cell migration. Inhibition of dynamin I and II GTPase with dynasore completely inhibited CCL3 stimulated chemotaxis in THP-1 cells, whereas the dynasore analogue dyngo-4a, which is a more potent inhibitor, showed reduced ability to inhibit CC-chemokine induced CTX. In contrast, dynasore was not able to block cell migration via CXCR4. The same activation/inhibition pattern was verified in activated-T-lymphocytes for different CC-and CXC-chemokines. Cell migration induced by CC- and CXC-receptors is not relying on active internalisation processes driven by dynamin since the blockade of internalisation does not affect migration, but they might rely on dynamin interaction with the cytoskeleton. We identify here a functional difference in how CC- and CXC-receptor migration is controlled, suggesting that specific signalling networks are being employed for different receptor classes and potentially specific therapeutic targets to prevent receptor migration can be identified.

Item Type: Article
Uncontrolled Keywords: chemokine receptor,chemotaxis,dynamin,signalling,internalization
Faculty \ School: Faculty of Science > School of Pharmacy
Faculty of Science
Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 11 Nov 2015 14:00
Last Modified: 07 May 2020 23:49
URI: https://ueaeprints.uea.ac.uk/id/eprint/55122
DOI: 10.1002/cbf.3131

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