Hepatocyte polarity
Open accessAbstract
Hepatocytes, like other epithelia, are situated at the interface between the organism's exterior and the underlying internal milieu and organize the vectorial exchange of macromolecules between these two spaces. To mediate this function, epithelial cells, including hepatocytes, are polarized with distinct luminal domains that are separated by tight junctions from lateral domains engaged in cell‐cell adhesion and from basal domains that interact with the underlying extracellular matrix. Despite these universal principles, hepatocytes distinguish themselves from other nonstriated epithelia by their multipolar organization. Each hepatocyte participates in multiple, narrow lumina, the bile canaliculi, and has multiple basal surfaces that face the endothelial lining. Hepatocytes also differ in the mechanism of luminal protein trafficking from other epithelia studied. They lack polarized protein secretion to the luminal domain and target single‐spanning and glycosylphosphatidylinositol‐anchored bile canalicular membrane proteins via transcytosis from the basolateral domain. We compare this unique hepatic polarity phenotype with that of the more common columnar epithelial organization and review our current knowledge of the signaling mechanisms and the organization of polarized protein trafficking that govern the establishment and maintenance of hepatic polarity. The serine/threonine kinase LKB1, which is activated by the bile acid taurocholate and, in turn, activates adenosine monophosphate kinase‐related kinases including AMPK1/2 and Par1 paralogues has emerged as a key determinant of hepatic polarity. We propose that the absence of a hepatocyte basal lamina and differences in cell‐cell adhesion signaling that determine the positioning of tight junctions are two crucial determinants for the distinct hepatic and columnar polarity phenotypes. © 2013 American Physiological Society. Compr Physiol 3:243‐287, 2013.
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E-cadherin participates in the organization of tight junctions, influencing polarization through the determination of apical and basolateral membrane areas.
“It further participates in the organization of tight junctions, thus influencing polarization through the determination of apical and basolateral membrane areas (Treyer and Müsch, 2013[40]).”
From Optimization of extracellular matrix for primary human hepatocyte cultures using mixed collagen-matrigel matrices (2023) · cites this paper as Treyer and Müsch, 2013[40]
E-cadherin is a key element of adherens junctions, mediating cell-cell contacts and outside-in signaling.
“E-cadherin is a key element of adherens junctions, thereby mediating cell-cell contacts and outside-in signaling.”
From Optimization of extracellular matrix for primary human hepatocyte cultures using mixed collagen-matrigel matrices (2023) · cites this paper as Treyer and Müsch, 2013[40]
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Schlegel, C. E., Weis, V. G., Knowles, B. C., Lapierre, L. A., Martı́n, M. G., Dickman, P. S., Goldenring, J. R., & Shub, M. D. (2017) · Digestive Diseases and Sciences · doi:10.1007/s10620-017-4867-5 · Cited by 29 · see citing works
The Inside-Out of End-Stage Liver Disease: Hepatocytes are the Keystone
Haep, N., Florentino, R. M., Squires, J. E., Bell, A. W., & Soto–Gutiérrez, A. (2021) · Seminars in Liver Disease · doi:10.1055/s-0041-1725023 · Cited by 31 · see citing works
Jia, Z., Cheng, Y., Jiang, X., Zhang, C., Wang, G., Xu, J., Li, Y., Peng, Q., & Gao, Y. (2020) · BioMed Research International · doi:10.1155/2020/6354183 · Cited by 28 · see citing works
RetractedAnisotropic expansion of hepatocyte lumina enforced by apical bulkheads
Belicová, L., Repnik, U., Delpierre, J., Gralinska, E., Seifert, S., Valenzuela, J. I., Morales-Navarrete, H. A., Franke, C., Räägel, H., Shcherbinina, E. Y., et al. (2021) · The Journal of Cell Biology · doi:10.1083/jcb.202103003 · Cited by 26 · see citing works
Ramakrishnan, V. M., Yang, J., Tien, K. T., McKinley, T. R., Bocard, B. R., Maijub, J. G., Burchell, P., Williams, S. K., Morris, M. E., Hoying, J. B., et al. (2015) · Scientific Reports · doi:10.1038/srep13231 · Cited by 27 · see citing works
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State-of-the-art advancements in Liver-on-a-chip (LOC): Integrated biosensors for LOC
Liu, M., Xiang, Y., Yang, Y., Long, X., Xiao, Z., Nan, Y., Jiang, Y., Qiu, Y., Huang, Q., & Ai, K. (2022) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2022.114758 · Cited by 27 · see citing works
Entry and Release of Hepatitis C Virus in Polarized Human Hepatocytes
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Cell–cell adhesion accounts for the different orientation of columnar and hepatocytic cell divisions
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Self-citation
- Authors
- Treyer, A., & Müsch, A.
- Affiliations
- Albert Einstein College of Medicine (US)
- ORCID
- Müsch, Anne
- Venue
- Comprehensive Physiology
- Publisher
- Wiley
- Published
- 2013-01
- Volume
- 3
- Issue
- 1
- Pages
- 243-287
- ISSN
- 2040-4603 (ISSN-L)
- PMC
- PMC3697931
- OpenAlex
- W4211245332
- Cited by
- 252
- References
- 511
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 10 · 2023: 18 · 2022: 32 · 2021: 35 · 2020: 33 · 2019: 22 · 2018: 20 · 2017: 19 · 2016: 20 · 2015: 12 · 2014: 14 · 2013: 1
- Type
- other
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Comprehensive physiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Public Health Service (R01KD064842-07)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK064842)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- hepatocyte polarity, epithelial polarity, bile canaliculi, tight junctions, transcytosis, LKB1, AMPK, PAR1, bile acid signaling, columnar epithelium, cell-cell adhesion, extracellular matrix
- MeSH terms
- Animals, Cell Adhesion, Humans, Intercellular Junctions, Liver, Phenotype, Cell Polarity, Hepatocytes
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