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Structural and functional hepatocyte polarity and liver disease.

Gissen P, Arias IM - J. Hepatol. (2015)

Bottom Line: Hepatocyte depolarization frequently occurs but is rarely recognized because hematoxylin-eosin staining does not identify the bile canaliculus.However, the molecular mechanisms underlying these defects are not well understood.Here we aim to provide an update on the key factors determining hepatocyte polarity and how it is affected in inherited and acquired diseases.

View Article: PubMed Central - PubMed

Affiliation: MRC Laboratory for Molecular Cell Biology, University College London, London, UK; UCL Institute of Child Health, London, UK; Great Ormond Street Hospital, London, UK. Electronic address: p.gissen@ucl.ac.uk.

No MeSH data available.


Related in: MedlinePlus

Intracellular pathways to canalicular and basolateral plasma membranes. Basolateral membrane proteins, including the LDL receptor, ASGP and other receptors, and NTCP, the bile acid transporter, traffic directly to the basolateral domain from which they are endocytosed and returned to the plasma membrane. The role of specific endosomal and subapical compartments in transcytosis is uncertain. Canalicular monotopic GPI-terminated proteins, mainly ectoenzymes (5NT, Aminopeptidase, CECAM105 etc) traffic from the TGN to the basolateral domain from which they undergo transcytosis through the recycling endosome (ARE) pool to the canalicular domain. In contrast, canalicular polytopic transporters ATP binding cassette proteins, such as ABCB1, ABCB11, ABCC2, and ABCB4, traffic from the TGN to the canalicular membrane either directly or via the large apical recycling endosomal (ARE) compartment from which they endogenously cycle to and from the canalicular membrane, or delivered into the degradation pathway to lysosomes. Segregation of apical and basolateral cargo proteins is thought to occur at the TGN although additional intracellular sorting sites have been proposed.
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f0015: Intracellular pathways to canalicular and basolateral plasma membranes. Basolateral membrane proteins, including the LDL receptor, ASGP and other receptors, and NTCP, the bile acid transporter, traffic directly to the basolateral domain from which they are endocytosed and returned to the plasma membrane. The role of specific endosomal and subapical compartments in transcytosis is uncertain. Canalicular monotopic GPI-terminated proteins, mainly ectoenzymes (5NT, Aminopeptidase, CECAM105 etc) traffic from the TGN to the basolateral domain from which they undergo transcytosis through the recycling endosome (ARE) pool to the canalicular domain. In contrast, canalicular polytopic transporters ATP binding cassette proteins, such as ABCB1, ABCB11, ABCC2, and ABCB4, traffic from the TGN to the canalicular membrane either directly or via the large apical recycling endosomal (ARE) compartment from which they endogenously cycle to and from the canalicular membrane, or delivered into the degradation pathway to lysosomes. Segregation of apical and basolateral cargo proteins is thought to occur at the TGN although additional intracellular sorting sites have been proposed.

Mentions: Embryologically, hepatoblasts are non-polarized and give rise to hepatocytes on stimulation by Oncostatin M (OSM) and TNF-alpha, and cholangiocytes, which are signaled by NOTCH and TGF-beta [11–13]. In mice, hepatocytes begin polarization on fetal day 14; however, mature BC do not appear until fetal day 21 [14,15]. Early canalicular network occurs by day 20 and rapid postnatal network formation occurs within two-three days after birth. During development, tight junctional complexes form, and apical and basolateral proteins including transporters become associated with specific plasma membrane domains (Fig. 3) [16]. These changes are associated with activation of 7-alpha-hydroxylase and synthesis of bile acids which may participate in regulating canalicular network formation similar to effects observed in hepatocyte cultures in which bile acids acting through a cAMP-Epac-MEK-AMPK pathway accelerate canalicular network formation (Fig. 4) [7].


Structural and functional hepatocyte polarity and liver disease.

Gissen P, Arias IM - J. Hepatol. (2015)

Intracellular pathways to canalicular and basolateral plasma membranes. Basolateral membrane proteins, including the LDL receptor, ASGP and other receptors, and NTCP, the bile acid transporter, traffic directly to the basolateral domain from which they are endocytosed and returned to the plasma membrane. The role of specific endosomal and subapical compartments in transcytosis is uncertain. Canalicular monotopic GPI-terminated proteins, mainly ectoenzymes (5NT, Aminopeptidase, CECAM105 etc) traffic from the TGN to the basolateral domain from which they undergo transcytosis through the recycling endosome (ARE) pool to the canalicular domain. In contrast, canalicular polytopic transporters ATP binding cassette proteins, such as ABCB1, ABCB11, ABCC2, and ABCB4, traffic from the TGN to the canalicular membrane either directly or via the large apical recycling endosomal (ARE) compartment from which they endogenously cycle to and from the canalicular membrane, or delivered into the degradation pathway to lysosomes. Segregation of apical and basolateral cargo proteins is thought to occur at the TGN although additional intracellular sorting sites have been proposed.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4582071&req=5

f0015: Intracellular pathways to canalicular and basolateral plasma membranes. Basolateral membrane proteins, including the LDL receptor, ASGP and other receptors, and NTCP, the bile acid transporter, traffic directly to the basolateral domain from which they are endocytosed and returned to the plasma membrane. The role of specific endosomal and subapical compartments in transcytosis is uncertain. Canalicular monotopic GPI-terminated proteins, mainly ectoenzymes (5NT, Aminopeptidase, CECAM105 etc) traffic from the TGN to the basolateral domain from which they undergo transcytosis through the recycling endosome (ARE) pool to the canalicular domain. In contrast, canalicular polytopic transporters ATP binding cassette proteins, such as ABCB1, ABCB11, ABCC2, and ABCB4, traffic from the TGN to the canalicular membrane either directly or via the large apical recycling endosomal (ARE) compartment from which they endogenously cycle to and from the canalicular membrane, or delivered into the degradation pathway to lysosomes. Segregation of apical and basolateral cargo proteins is thought to occur at the TGN although additional intracellular sorting sites have been proposed.
Mentions: Embryologically, hepatoblasts are non-polarized and give rise to hepatocytes on stimulation by Oncostatin M (OSM) and TNF-alpha, and cholangiocytes, which are signaled by NOTCH and TGF-beta [11–13]. In mice, hepatocytes begin polarization on fetal day 14; however, mature BC do not appear until fetal day 21 [14,15]. Early canalicular network occurs by day 20 and rapid postnatal network formation occurs within two-three days after birth. During development, tight junctional complexes form, and apical and basolateral proteins including transporters become associated with specific plasma membrane domains (Fig. 3) [16]. These changes are associated with activation of 7-alpha-hydroxylase and synthesis of bile acids which may participate in regulating canalicular network formation similar to effects observed in hepatocyte cultures in which bile acids acting through a cAMP-Epac-MEK-AMPK pathway accelerate canalicular network formation (Fig. 4) [7].

Bottom Line: Hepatocyte depolarization frequently occurs but is rarely recognized because hematoxylin-eosin staining does not identify the bile canaliculus.However, the molecular mechanisms underlying these defects are not well understood.Here we aim to provide an update on the key factors determining hepatocyte polarity and how it is affected in inherited and acquired diseases.

View Article: PubMed Central - PubMed

Affiliation: MRC Laboratory for Molecular Cell Biology, University College London, London, UK; UCL Institute of Child Health, London, UK; Great Ormond Street Hospital, London, UK. Electronic address: p.gissen@ucl.ac.uk.

No MeSH data available.


Related in: MedlinePlus