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Mouse MCP1 C-terminus inhibits human MCP1-induced chemotaxis and BBB compromise.

ABSTRACT: Compared to the rodent monocyte chemoattractant protein 1 (MCP1/CCL2), the human MCP1 lacks a C-terminal extension. Although the function of this C-extension is not entirely defined, in previous work we reported that it decreases the chemotactic properties of mouse MCP1. To determine if this function is specific to the rodent chemokine, or if the C-terminal extension has the ability to regulate chemotactic potency to MCP1 in general, we generated a chimeric protein consisting of human MCP1 fused to the mouse MCP1 C-terminal fragment. We found that mouse MCP1 C-terminus significantly decreased the chemotactic potency of human MCP1 and diminished the blood brain barrier compromise normally induced by the human protein. Not only did mouse MCP1 C-terminus inhibit human MCP1-induced Rac1 activation and formation of lamellipodia, it also disrupted the staining pattern of ZO-1 at cell-cell borders and prevented human MCP1-induced F-actin formation in brain microvascular endothelial cells. Additionally, the MCP1 C-terminus dramatically decreased human MCP1-induced activation of ERM proteins in endothelial cells. These findings confirm that the rodent C-terminal MCP1 extension acts as a rheostat for MCP1 functions and suggest that potentially in humans another protein or protein complex may assume a similar regulatory function.

SUBMITTER: Yao Y

PROVIDER: S-EPMC3129361 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Mouse MCP1 C-terminus inhibits human MCP1-induced chemotaxis and BBB compromise.

Yao Yao Y Tsirka Stella E SE

Journal of neurochemistry 20110613 2

Compared to the rodent monocyte chemoattractant protein 1 (MCP1/CCL2), the human MCP1 lacks a C-terminal extension. Although the function of this C-extension is not entirely defined, in previous work we reported that it decreases the chemotactic properties of mouse MCP1. To determine if this function is specific to the rodent chemokine, or if the C-terminal extension has the ability to regulate chemotactic potency to MCP1 in general, we generated a chimeric protein consisting of human MCP1 fused ...[more]

PMID: 21615737

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Dataset Information

Mouse MCP1 C-terminus inhibits human MCP1-induced chemotaxis and BBB compromise.

Publications

Mouse MCP1 C-terminus inhibits human MCP1-induced chemotaxis and BBB compromise.

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