Review
Crosstalk of tight junction components with signaling pathways

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Abstract

Tight junctions (TJs) regulate the passage of ions and molecules through the paracellular pathway in epithelial and endothelial cells. TJs are highly dynamic structures whose degree of sealing varies according to external stimuli, physiological and pathological conditions. In this review we analyze how the crosstalk of protein kinase C, protein kinase A, myosin light chain kinase, mitogen-activated protein kinases, phosphoinositide 3-kinase and Rho signaling pathways is involved in TJ regulation triggered by diverse stimuli. We also report how the phosphorylation of the main TJ components, claudins, occludin and ZO proteins, impacts epithelial and endothelial cell function.

Abbreviations

ANP
atrial natriuretic peptide
ARPE-19
human retinal pigment epithelial cell line
AsPC-1
human pancreatic cancer cell line
BAEC
bovine aortic endothelial cells (primary culture)
BBB
blood–brain barrier
BPAEC
bovine pulmonary artery endothelial cell line
BRB
blood retinal barrier
C3
transferase from Clostridium botulinum
Caco-2
human colonic adenocarcinoma cell line
CAPAN-2
human pancreas epithelial cell line
CK2
casein kinase 2
Con8
rat mammary tumor epithelial cell line
CRIB
Cdc42 and Rac interaction binding
CRM1
chromosomal region maintenance 1
94D
mouse cortical collecting Duct epithelial cell line
DAG
diacylglycerol
DHT
dihydrotestosterone
DiC8
phosphatidyl inositol 3,4,5-triphosphate
E2
estradiol
EcN
Escherichia coli Nissle
ECT2
A guanine nucleotide exchange factor
EGF
epidermal growth factor
EGTA
ethylene glycol tetraacetic acid
EHEC
enterohemorrhagic Escherichia coli
EMT
epithelial mesenchymal transition
EPEC
enteropathogenic Escherichia coli
ERK
extracellular signal-regulated kinase
FAK
focal adhesion kinase
FBS
fetal bovine serum
FF
freeze–fracture
FGF
fibroblast growth factor
FHHNC
familial hypomagnesemia with hypercalciuria and nephrocalcinosis
GC
guanylate cyclase
GEF-H1
A guanine nucleotide exchange factor
GPI
glycosyl phosphatidyl inositol
GSK-3β
glycogen synthase kinase 3 beta
HBMEC
human brain microvascular endothelial cell line
HepG2
hepatic cell line
HGF
hepatocyte growth factor
HMEC
human dermal microvascular endothelial cell line
HPAEC
human pulmonary artery endothelial cell line
HT-29
human colon adenocarcinoma cell line
HUVEC
human umbilical cord endothelial cell line
ICM
inner cell mass
IEC-6
rat small intestine epithelial cell line
IFNγ
interferon gamma
IL-17
interleukine 17
JNK
c-Jun N-terminal kinase
LC
low calcium (1–5 μM Ca2+)
Lgl
lethal giant larva
LLC-PK1
pig renal cell line
LPA
lysophosphatidic acid
MAGUK
membrane-associated guanylate kinase
MAPK
mitogen-activated protein kinase
MARCKs
myristoylated alanine-rich C kinase susbstrate
MDCK
Madin–Darby canine kidney cell line
2ME
2 methoxyestradiol
ML7
1-(5-iodonaphthalene 1-sulfonyl)-1H-hexadydro-1,4-iazepine HCl
ML9
1-(5-cloronaphthalene 1-sulfonyl)-1H-hexadydro-1,4-diazepine HCl
MLC2
regulatory myosin light chain
MYPT
myosin phosphatase target subunit
NC
normal calcium (1.8 mM Ca2+)
NES
nuclear export signal
NLS
nuclear localization signal
NO
nitric oxide
NOS
nitric oxide synthase
N-WASP
neuronal Wiskott Aldrich syndrome protein
OmpA
outer membrane protein A
PAR-2
protease-activated receptor 2
PB1
Phox and Bem1p
PC1
Hamster pancreatic ductal carcinoma cell line
PHAII
pseudohypoaldosteronism type two
PI3K
phosphoinositide 3-kinase
PKA
protein kinase A
PKC
protein kinase C
PKG
protein kinase G
PLC γ
phospholipase C gamma
PLGF-1
placental growth factor 1
PLF
polyp-like foci
PMA
phorbol 12-myristate 13-acetate
POI
post-flight orthostatic intolerance
PP1
protein phosphatase 1
PP2A
protein phosphatase 2A
PP2B
protein phosphatase 2B
REC
retinal endothelial cells
RLE
rat lung endothelial cell line
ROMK
apical potassium channel
ROS
reactive oxygen species
SARA
Smad anchor for receptor activation protein
SGLT1
sodium glucose cotransporter
T-84
human colorectal carcinoma cell line
TAL
thick ascending limb of Henle
TEM
transmission electron microscopy
TER
transepithelial electrical resistance
TGFβ
transforming growth factor beta
TJ
tight junction
TLR2
Toll-like receptor 2
TNFα
tumor necrosis factor alpha
TPA
12-O-tetradecanoyl phorbol-13-acetate
VAC
vacuolar apical compartment
VE-cadherin
endothelial cadherin
VEGF
vascular endothelial growth factor
VEGFR-2
vascular endothelial growth factor receptor
WB-F344
rat liver epithelial cell line
WNK
with no lysine kinase
Zot
zonula occludens toxin

Keywords

Tight junction
Claudin
Occludin
ZO-1
MAPK
PI3K
AKT
Rho
MLCK
PKC
PKA
PKG

Cited by (0)

1

Rocio Tapia and David Chamorro contributed equally.

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