Endocytosis as an Essential Process in Liver Function and Pathology

Schroeder, Barbara; McNiven, Mark A.

doi:10.1002/9780470747919.ch7

Cited by 6 publications

(5 citation statements)

References 204 publications

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“…Clathrin‐mediated endocytosis in hepatocytes and other epithelial cells involves the assembly of a structural scaffold along the plasma membrane (PM) composed of clathrin, adaptors, and other proteins that sequester surface receptors and deform the lipid bilayer into an invaginating bud 1‐4. These coated invaginations are believed to be liberated from the PM by the combined efforts of lipid‐modifying enzymes,5, 6 the actin‐myosin cytoskeleton,7, 8 and the large guanosine triphosphate (GTP)ase dynamin 9‐12.…”

mentioning

confidence: 99%

Hepatocytes internalize trophic receptors at large endocytic “Hot Spots”

2011

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Clathrin-mediated endocytosis in mammalian epithelial cells is believed to require the synergistic action of structural coat proteins and mechanochemical enzymes to deform and sever the plasma membrane (PM) into discreet vesicles. It is generally believed that the formation of clathrin-coated pits in epithelial cells occurs randomly along the apical and basolateral plasma membranes. In this study we have visualized the endocytic machinery in living hepatocytes using green fluorescent protein GFP–tagged dynamin, a large mechanochemical GTPase implicated in the liberation of nascent vesicles from the plasma membrane and a variety of internal membrane compartments. Confocal microscopy of living cells expressing the epithelial isoform of GFP-tagged dynamin [Dyn2-GFP] revealed a distribution along the ventral PM in discreet vesicle-like puncta or in large (2–10 μm) tubulo-reticular plaques. Remarkably, these large structures are dynamic as they form and then disappear, while generating large numbers of motile endocytic vesicles with which dynamin associates. Inhibiting dynamin function by microinjection of purified dynamin antibodies increases the number and size of the tubulo-reticular plaques. Importantly, these “hot spots” sequester specific trophic receptors and cognate ligands such as the TfR1, but not the TfR2. These findings suggest that hepatocytes sequester or pre-recruit both structural and enzymatic components of the clathrin-based endocytic machinery to functional “hot spots,” from which large numbers of coated pits form and vesicles are generated. This process may mimic the endocytic organization found at the synapse in neuronal cells.

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confidence: 99%

Hepatocytes internalize trophic receptors at large endocytic “Hot Spots”

2011

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“…As shown in the cartoon (right), the canalicular domain is dominated by ectoenzymes and numerous transporters that shuttle water, bile acids, lipids, and other organic and inorganic molecules across the membrane and into the bile canaliculus. Electron micrographs (magnification of 9,100) are reprinted with permission from Schroeder and McNiven (2009). AQP, aquaporin; MATE-1, multidrug and extrusion protein 1; AP-N, alanine aminopeptidase.…”

Section: The Hepatocyte As a Protein And Biliary Secretion Factorymentioning

confidence: 99%

The cell biology of the hepatocyte: A membrane trafficking machine

Schulze

Schott

Casey

et al. 2019

Journal of Cell Biology

139

102

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The liver performs numerous vital functions, including the detoxification of blood before access to the brain while simultaneously secreting and internalizing scores of proteins and lipids to maintain appropriate blood chemistry. Furthermore, the liver also synthesizes and secretes bile to enable the digestion of food. These diverse attributes are all performed by hepatocytes, the parenchymal cells of the liver. As predicted, these cells possess a remarkably well-developed and complex membrane trafficking machinery that is dedicated to moving specific cargos to their correct cellular locations. Importantly, while most epithelial cells secrete nascent proteins directionally toward a single lumen, the hepatocyte secretes both proteins and bile concomitantly at its basolateral and apical domains, respectively. In this Beyond the Cell review, we will detail these central features of the hepatocyte and highlight how membrane transport processes play a key role in healthy liver function and how they are affected by disease.

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“…The mechanisms by which lipid bilayers are deformed and vesiculated to support the endocytic and secretory pathways in the hepatocyte are well studied (for reviews see6, 7). Although LDs are encased in a lipid monolayer, it is reasonable to predict that many components utilized to tubulate the plasma membrane, endosomes, and the Golgi apparatus could also be recruited to LDs to mediate LD breakdown.…”

Section: Membrane Dynamics Contributing To Lipid Droplet Vesiculationmentioning

confidence: 99%