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Arias, MD
Triple Emeritus: Professor of Medicine (Albert Einstein College of Medicine);
Professor of Physiology and Medicine (Tufts University School of Medicine and
Senior Scientist (National Institute of Health)
Bile Canaliculi
Scan Electron Microscope
Canaliculi cast
Liver Tissue Section
(ABCB1 staining)
Loss of polarity results in bile secretory failure (cholestasis) and cell death.
Day2
Day3
Day4
Occludin
ABCB1
Occludin
ABCB1
Occludin
ABCB1
Occludin
ABCB1
Day5
Day6
***
*** p<0.001
** p<0.01
***
***
***
Occludin
ABCB1
**
Occludin
ABCB1
canaliculi
Hepatocytes
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Ser 431 P
LKB1
STRAD
Adaptor protein
AMPK
AMPK
AMPK
MDCK cells
Day 1
Day 1
LKB1
Phos-LKB1
AMPK
Phos-AMPK
-actin
-actin
PNAS 2010
Fig2: Dynamic of protein levels of total and phosphorylated LKB1 and AMPK. A: Western blot for LKB1, AMPK, phos-LKB1
and phos-AMPK. B, C: Densitometery measurements (n= 4).
8-Br-cAMP
taurocholate
CPT-cAMP
cAMP
6-Bnz-cAMP
PKI
Epac
LKB1
PKA
canalicular trafficking
AMP
AICAR
ATP
AMPK
AMPK-P
ATP
PP2C
cell
polarization
catabolism
lipid synthesis
protein synthesis
AMP
cell growth
Forskolin
Metformin
2-DG
AICAR
Ser 431
MO25
LKB1
STRAD
KD-LKB1 adenovirus
Thr172 P
AMPK
AMPK
AMPK
Myc-DN-AMPK adenovirus
Forskolin
Occludin
ABCB1
Occludin
ABCB1
2DG
AICAR
Metformin
Occludin
ABCB1
*
*
Occludin
ABCB1
**
*
*
*
Occludin
ABCB1
GFP
Occludin
ABCB1
GFP
ABCB1
***
LKB1
AMPK
LKB1-KD
Myc-DN-AMPK
LKB1
ABCB1
Myc
ABCB1
***
Canalicular
Formation
Transmission EM
Day 1
Day6
Day2
Day 2
PNAS 2012
Day 6
Fragmented
Tubular
Tubular / vesicular
100
% of cells
80
60
40
20
Tubular and big vesicles
PNAS 2012
0
Day 0
Fragmented
Tubular
Tubular and big vesicles
Tubular
Day 1
Day 2
Day 3
Fragmented
Day 4
Day 5
Day 6
Mfn1, 2
Opa1
DRP1
Mitochondrial fission and fusion protein expressions during canalicular network formation
DRP-1
Phos DRP-1
Actin
Mfn-1
Mfn-2
Actin
Cox IV
Hsp60
Tom20
Actin
PNAS 2012
PNAS 2012
PNAS 2012
PNAS 2012
PNAS 2012
EPAC/MEK
Bile acid
LKB1
NAD-Sirt1-PGCa-FOXO
Thr172
Mito ATP/ FUSION
AMPK
Polarity