Blood-Brain Barrier and Immune Cell Transmigration: CCL2/MCP-1 Signaling Pathways

Click on one of the other molecules below to see the signaling pathways activated by that molecule and the changes it induces in the integrity of the blood-brain barrier (BBB). Click on Overview to see the generalized process of immune cell transmigration across the BBB during neuroinflammation.

CCL2/MCP-1
CCL2/MCP-1
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CCR2
CCR2
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G protein
G protein
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RhoA
RhoA
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ROCK
ROCK
MLCP
MLCP
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MLC2
MLC2
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MLCK
MLCK
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MLC2
MLC2
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Stress Fiber Formation
Increased Centripetal Tension
Cell Retraction

Stress Fiber Formation
Increased Centripetal Tension
Cell Retraction

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Occludin
Occludin
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ZO-1
ZO-1
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ZO-2
ZO-2
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F-Actin
F-Actin
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Occludin
Occludin
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Receptor Endocytosis

Receptor Endocytosis

ZO-1
ZO-1
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Afadin/AF-6
Afadin/AF-6
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Claudins
Claudins
Claudins
Claudins

Receptor Endocytosis

Receptor Endocytosis

JAMs
JAMs
ZO-1
ZO-1
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Afadin/AF-6
Afadin/AF-6
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Cingulin
Cingulin
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JAMs
JAMs

Relocate to
Apical Surface

Relocate to
Apical Surface

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VE-Cadherin
VE-Cadherin
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p120
p120
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beta-Catenin
beta-Catenin
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alpha-Catenin
alpha-Catenin
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PLC-beta
PLC-beta
PIP2
PIP2
IP3
IP3
DAG
DAG
PKC alpha
PKC zeta
PKC alpha
PKC zeta
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Occludin
Occludin
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ZO-1
ZO-1
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F-Actin
F-Actin
ZO-2
ZO-2
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Occludin
Occludin
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Receptor Endocytosis

Receptor Endocytosis

Afadin/AF-6
Afadin/AF-6
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ZO-1
ZO-1
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Claudins
Claudins
Claudins
Claudins

Receptor Endocytosis

Receptor Endocytosis

JAMs
JAMs
Cingulin
Cingulin
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Afadin/AF-6
Afadin/AF-6
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ZO-1
ZO-1
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VE-Cadherin
VE-Cadherin
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p120
p120
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beta-Catenin
beta-Catenin
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alpha-Catenin
alpha-Catenin
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Brain Tissue
Brain Tissue
Brain Endothelial Cells
Brain Endothelial Cells

Overview of CCL2/MCP-1 Signaling and its Primary Biological Effects in Brain Endothelial Cells

The BBB is a selective diffusion barrier that is composed of specialized endothelial cells (ECs) that are linked by tight junctions (TJs) and adherens junctions (AJs). These junction complexes can be remodeled during neuroinflammation to form interendothelial gaps that peripheral immune cells will pass through to enter the central nervous system (CNS). The chemokine CCL2/MCP-1 is elevated in the CNS during neuroinflammatory conditions and is a potent inducer of BBB disruption. CCL2/MCP-1 binds to CCR2 on brain ECs to initiate intracellular signaling cascades that result in the dynamic reorganization of junction complexes and EC retraction. CCL2/MCP-1 induces the phosphorylation of TJ proteins, resulting in their disassembly and/or redistribution from the cell border. JAM proteins will relocate to the apical surface of ECs where they participate in adhesive interactions with leukocyte integrins. CCL2/MCP-1 signaling also induces reorganization of F-Actin microfilaments into stress fibers, which increases centripetal tension inside the cell resulting in cell retraction.

To learn more, please visit our CC Chemokines and Receptors Research Area

Blood-Brain Barrier and Immune Cell Transmigration: CCL2/MCP-1 Signaling Pathways background image 1