Blood-Brain Barrier and Immune Cell Transmigration: ICAM-1/CD54 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.
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Integrin alpha 4 beta 1
(VLA-4)
(VLA-4)
Integrin alpha 4 beta 1
(VLA-4)
(VLA-4)
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Integrin alpha L beta 2
(LFA-1)
(LFA-1)
Integrin alpha L beta 2
(LFA-1)
(LFA-1)
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VCAM-1/CD106
VCAM-1/CD106
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ICAM-1/CD54
ICAM-1/CD54
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ERM
ERM
PLC-gamma
PLC-gamma
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PIP2
PIP2
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DAG
DAG
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PKC alpha
PKC alpha
RhoA
RhoA
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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Ca2+
Ca2+
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PKC
PKC
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Src
Src
Cortactin
Cortactin
NADPH
Oxidase
Oxidase
NADPH
Oxidase
Oxidase
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NOx
NOx
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
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PYK2/FAK2
PYK2/FAK2
ZO-1
ZO-1
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ZO-2
ZO-2
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Cingulin
Cingulin
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F-Actin
F-Actin
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Occludin
Occludin
Afadin/AF-6
Afadin/AF-6
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Claudins
Claudins
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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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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
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IP3
IP3
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Ca2+
Ca2+
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IP3 Receptor
IP3 Receptor
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Ca2+/Calmodulin
Ca2+/Calmodulin
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CaMKK
CaMKK
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AMPK
AMPK
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eNOS
eNOS
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PKC
PKC
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NADPH
Oxidase
Oxidase
NADPH
Oxidase
Oxidase
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NOx
NOx
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
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RhoA
RhoA
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PI 3-Kinase
PI 3-Kinase
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Akt
Akt
HSP27
HSP27
Ca2+
ATPase
ATPase
Ca2+
ATPase
ATPase
Stress Fiber
Formation
Increased
Centripetal
Tension
Cell Retraction
Stress Fiber
Formation
Increased
Centripetal
Tension
Cell Retraction
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Occludin
Occludin
Occludin
Occludin
Receptor Endocytosis
Receptor Endocytosis
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Afadin/AF-6
Afadin/AF-6
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F-Actin
F-Actin
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Claudins
Claudins
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JAMs
JAMs
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Cingulin
Cingulin
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VE-Cadherin
VE-Cadherin
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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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VE-Cadherin
VE-Cadherin
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Receptor Endocytosis
Receptor Endocytosis
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Stress Fiber Formation
Increased Centripetal Tension
Cell Retraction
Stress Fiber Formation
Increased Centripetal Tension
Cell Retraction
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Leukocyte
Leukocyte
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Brain Endothelial Cells
Brain Endothelial Cells
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ZO-1
ZO-1
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ZO-1
ZO-1
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ZO-1
ZO-1
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ZO-1
ZO-1
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Afadin/AF-6
Afadin/AF-6
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Cingulin
Cingulin
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Overview of ICAM-1/CD54 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. Intercellular Adhesion Molecule 1 (ICAM-1/CD54) is an Ig-like adhesion receptor that binds the leukocyte Integrin alpha 4 beta 1 (LFA-1). This interaction induces clustering of ICAM-1/CD54 and activation of intracellular signaling pathways that induce phosphorylation of TJ proteins, resulting in their disassembly and/or redistribution from the cell border. Specifically, ICAM-1/CD54 signaling promotes endocytosis of Occludin and VE-Cadherin. Additionally, ICAM-1/CD54 signaling 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.
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