Limits...
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

Suggested model for intracellular trafficking pathways of plasma membrane proteins in hepatocytes. Trafficking of polytopic apical proteins from the apical recycling endosome (ARE) compartment to the canalicular membrane is enhanced by taurocholate and cAMP, requires PI-3K, Rab11a, and Fip1 and 2 adaptor proteins, Myosin 5b and energy in the form of ATP. Endocytosis of the apical membrane proteins is clathrin-mediated and requires HAX-1, Myosin light chain kinase MLCK and most likely many other unidentified components. All intracellular trafficking requires an intact dynamic microtubular system, subsequent transfer of cargo-containing endosomes to the pericanalicular actin system, and binding to Syntaxin 3 and possibly other SNARE proteins which facilitate endosome fusion with the apical membrane. Apical membrane targeting pathways in blue. Basolateral membrane targeting pathways in red. Bile canaliculus (BC), common recycling endosome (CRE), endoplasmic reticulum (ER).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4582071&req=5

f0025: Suggested model for intracellular trafficking pathways of plasma membrane proteins in hepatocytes. Trafficking of polytopic apical proteins from the apical recycling endosome (ARE) compartment to the canalicular membrane is enhanced by taurocholate and cAMP, requires PI-3K, Rab11a, and Fip1 and 2 adaptor proteins, Myosin 5b and energy in the form of ATP. Endocytosis of the apical membrane proteins is clathrin-mediated and requires HAX-1, Myosin light chain kinase MLCK and most likely many other unidentified components. All intracellular trafficking requires an intact dynamic microtubular system, subsequent transfer of cargo-containing endosomes to the pericanalicular actin system, and binding to Syntaxin 3 and possibly other SNARE proteins which facilitate endosome fusion with the apical membrane. Apical membrane targeting pathways in blue. Basolateral membrane targeting pathways in red. Bile canaliculus (BC), common recycling endosome (CRE), endoplasmic reticulum (ER).

Mentions: Proper endosomal trafficking and recycling of proteins to all plasma membrane domains requires an intact actin and microtubular cytoskeletal system [74,75]. In particular, dynamic microtubules mediate trafficking of secreted and canalicular proteins [76]. Newly synthesized ABCB11, the canalicular bile acid transporter, and other canalicular ABC transporters traffic from the TGN along microtubules [77]. However, microtubules do not attach to the canalicular membrane and their cargo endosomes are transferred to the pericanalicular actin system (Fig. 5). The complete mechanism for cargo transfer is not known; however, microtubules become associated with actin through a pericanalicular actin-binding complex containing CLIP170, IQGap, APC, Hax-1, and cortactin proteins [78]. Live cell imaging studies reveal that selective plasma membrane localization of transporter proteins is predominantly due to the localization of specific docking proteins. In polarized WIF-B cells, ABCB11 and ABCB1 were shown to traffic along microtubules throughout the cell but only attach to sites on the canalicular membrane [77]. The docking site has been proposed to be Syntaxin 3 that facilitates fusion of protein sorting vesicles with the inner leaflet of the canalicular membrane [79,80]. Radixin also participates in this process and links some cargo molecules such as ABCC2, to the pericanalicular actin system [81]. Radixin knockout mice manifest impaired ABCC2 localization to the canalicular domain which becomes progressively devoid of microvilli resulting in hepatocyte injury [82]. Assembly and disassembly of short actin filaments involved in endosomal transport are under the control of formin [83]. Work in HepG2 cell line demonstrated the requirement for INF2, CDC42 and transmembrane protein MAL2, for trafficking of canalicular membrane proteins in the transcytotic pathway.


Structural and functional hepatocyte polarity and liver disease.

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

Suggested model for intracellular trafficking pathways of plasma membrane proteins in hepatocytes. Trafficking of polytopic apical proteins from the apical recycling endosome (ARE) compartment to the canalicular membrane is enhanced by taurocholate and cAMP, requires PI-3K, Rab11a, and Fip1 and 2 adaptor proteins, Myosin 5b and energy in the form of ATP. Endocytosis of the apical membrane proteins is clathrin-mediated and requires HAX-1, Myosin light chain kinase MLCK and most likely many other unidentified components. All intracellular trafficking requires an intact dynamic microtubular system, subsequent transfer of cargo-containing endosomes to the pericanalicular actin system, and binding to Syntaxin 3 and possibly other SNARE proteins which facilitate endosome fusion with the apical membrane. Apical membrane targeting pathways in blue. Basolateral membrane targeting pathways in red. Bile canaliculus (BC), common recycling endosome (CRE), endoplasmic reticulum (ER).
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

f0025: Suggested model for intracellular trafficking pathways of plasma membrane proteins in hepatocytes. Trafficking of polytopic apical proteins from the apical recycling endosome (ARE) compartment to the canalicular membrane is enhanced by taurocholate and cAMP, requires PI-3K, Rab11a, and Fip1 and 2 adaptor proteins, Myosin 5b and energy in the form of ATP. Endocytosis of the apical membrane proteins is clathrin-mediated and requires HAX-1, Myosin light chain kinase MLCK and most likely many other unidentified components. All intracellular trafficking requires an intact dynamic microtubular system, subsequent transfer of cargo-containing endosomes to the pericanalicular actin system, and binding to Syntaxin 3 and possibly other SNARE proteins which facilitate endosome fusion with the apical membrane. Apical membrane targeting pathways in blue. Basolateral membrane targeting pathways in red. Bile canaliculus (BC), common recycling endosome (CRE), endoplasmic reticulum (ER).
Mentions: Proper endosomal trafficking and recycling of proteins to all plasma membrane domains requires an intact actin and microtubular cytoskeletal system [74,75]. In particular, dynamic microtubules mediate trafficking of secreted and canalicular proteins [76]. Newly synthesized ABCB11, the canalicular bile acid transporter, and other canalicular ABC transporters traffic from the TGN along microtubules [77]. However, microtubules do not attach to the canalicular membrane and their cargo endosomes are transferred to the pericanalicular actin system (Fig. 5). The complete mechanism for cargo transfer is not known; however, microtubules become associated with actin through a pericanalicular actin-binding complex containing CLIP170, IQGap, APC, Hax-1, and cortactin proteins [78]. Live cell imaging studies reveal that selective plasma membrane localization of transporter proteins is predominantly due to the localization of specific docking proteins. In polarized WIF-B cells, ABCB11 and ABCB1 were shown to traffic along microtubules throughout the cell but only attach to sites on the canalicular membrane [77]. The docking site has been proposed to be Syntaxin 3 that facilitates fusion of protein sorting vesicles with the inner leaflet of the canalicular membrane [79,80]. Radixin also participates in this process and links some cargo molecules such as ABCC2, to the pericanalicular actin system [81]. Radixin knockout mice manifest impaired ABCC2 localization to the canalicular domain which becomes progressively devoid of microvilli resulting in hepatocyte injury [82]. Assembly and disassembly of short actin filaments involved in endosomal transport are under the control of formin [83]. Work in HepG2 cell line demonstrated the requirement for INF2, CDC42 and transmembrane protein MAL2, for trafficking of canalicular membrane proteins in the transcytotic pathway.

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