Blood-Brain Barrier and Immune Cell Transmigration: VCAM-1/CD106 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.

Integrin alpha 4 beta 1
(VLA-4)
Integrin alpha 4 beta 1
(VLA-4)
Integrin alpha L beta 2
(LFA-1)
Integrin alpha L beta 2
(LFA-1)
VCAM-1/CD106
VCAM-1/CD106
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ICAM-1/CD54
ICAM-1/CD54
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ERM
ERM
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L-Type
Ca2+ Channel
L-Type
Ca2+ Channel
Ca2+
Ca2+
↑[Ca2+]i
↑[Ca2+]i
PKC
PKC
Src
Src
PLC-gamma
PLC-gamma
PIP2
PIP2
IP3
IP3
IP3 Receptor
IP3 Receptor
Ca2+
Ca2+
DAG
DAG
PKC alpha
PKC alpha
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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

PI 3-Kinase
PI 3-Kinase
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Rac1
Rac1
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PAK
PAK
Ca2+
Ca2+
NADPH
Oxidase
NADPH
Oxidase
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NOx
NOx
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p67phox
p67phox
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p40phox
p40phox
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p47phox
p47phox
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p22phox
p22phox
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ROS
ROS
MMP-2
MMP-9
MMP-2
MMP-9
PYK2/FAK2
PYK2/FAK2
SHP-2
SHP-2
F-Actin
F-Actin
ZO-1
ZO-1
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ZO-2
ZO-2
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Occludin
Occludin
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Tight Junction Protein
Degradation

Tight Junction Protein
Degradation

Afadin/AF-6
Afadin/AF-6
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ZO-1
ZO-1
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Claudins
Claudins
Afadin/AF-6
Afadin/AF-6
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ZO-1
ZO-1
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Cingulin
Cingulin
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JAMs
JAMs
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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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p120
p120
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beta-Catenin
beta-Catenin
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alpha-Catenin
alpha-Catenin
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VE-Cadherin
VE-Cadherin
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Receptor Endocytosis

Receptor Endocytosis

Leukocyte
Leukocyte
Brain Endothelial Cells
Brain Endothelial Cells

Overview of VCAM-1/CD106 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). Engagement of adhesion molecules on the surface of ECs by leukocyte integrins activates diverse signaling pathways in ECs that result in the dynamic reorganization of junction complexes and EC retraction. Vascular Cell Adhesion Molecule 1 (VCAM-1/CD106) is an Ig-like adhesion receptor that binds the leukocyte Integrin alpha 4 beta 1 (VLA-4). This induces clustering of VCAM-1/CD106 and activation of intracellular signaling pathways that induce phosphorylation of TJ proteins, resulting in their disassembly and/or redistribution from the cell border. Additionally, VCAM-1/CD106 signaling promotes the production of matrix metalloproteases (MMPs) that degrade junction proteins. VCAM-1/CD54 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 Immunoglobulin Superfamily CAMs Research Area.

Blood-Brain Barrier and Immune Cell Transmigration: VCAM-1/CD106 Signaling Pathways background image 1