Intracellular lumina and bile canaliculi in rat hepatocytes in vitro — a cytochemical study

Rémy, Lionel; Chalvet, Christine; Ripert, Jean-Pierre; Gérolami, A

doi:10.1016/s0065-1281(89)80103-5

Cited by 6 publications

(2 citation statements)

References 9 publications

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“…Moreover, as noted above, cAMP stimulates transport of sphingolipids to the bile canalicular membrane, which similarly is accompanied by an enlargement of the apical membrane surface [24]. Finally, an elevation of intracellular cAMP enhances the formation of canalicular vacuoles in single hepatocytes that do no longer maintain a polarized apical membrane [161]. Also this observation is probably related to an enhanced membrane trafficking to the canalicular membrane (see Scheme 1).…”

Section: Involvement Of Intracellular Signaling In Hepatic Apical Lipmentioning

confidence: 65%

Mechanisms and functional features of polarized membrane traffic in epithelial and hepatic cells

Zegers

Hoekstra

1998

Biochemical Journal

135

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Epithelial cells express plasma-membrane polarity in order to meet functional requirements that are imposed by their interaction with different extracellular environments. Thus apical and basolateral membrane domains are distinguished that are separated by tight junctions in order to maintain the specific lipid and protein composition of each domain. In hepatic cells, the plasma membrane is also polarized, containing a sinusoidal (basolateral) and a bile canalicular (apical)-membrane domain. Relevant to the biogenesis of these domains are issues concerning sorting, (co-)transport and regulation of transport of domain-specific membrane components. In epithelial cells, specific proteins and lipids, destined for the apical membrane, are sorted in the trans-Golgi network (TGN), which involves their sequestration into cholesterol/sphingolipid 'rafts', followed by 'direct' transport to the apical membrane. In hepatic cells, a direct apical transport pathway also exists, as revealed by transport of sphingolipids from TGN to the apical membrane. This is remarkable, since in these cells numerous apical membrane proteins are 'indirectly' sorted, i.e. they are first transferred to the basolateral membrane prior to their subsequent transcytosis to the apical membrane. This raises intriguing questions as to the existence of specific lipid rafts in hepatocytes. As demonstrated in studies with HepG2 cells, it has become evident that, in hepatic cells, apical transport pathways can be regulated by protein kinase activity, which in turn modulates cell polarity. Finally, an important physiological function of hepatic cells is their involvement in intracellular transport and secretion of bile-specific lipids. Mechanisms of these transport processes, including the role of multidrug-resistant proteins in lipid translocation, will be discussed in the context of intracellular vesicular transport. Taken together, hepatic cell systems provide an important asset to studies aimed at elucidating mechanisms of sorting and trafficking of lipids (and proteins) in polarized cells in general.

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Section: Involvement Of Intracellular Signaling In Hepatic Apical Lipmentioning

confidence: 65%

Mechanisms and functional features of polarized membrane traffic in epithelial and hepatic cells

Zegers

Hoekstra

1998

Biochemical Journal

135

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“…In the absence of cell–cell contacts, the exocytosis of VACs could be induced by the addition of cAMP ( 11 ). Moreover, cAMP was reported to increase the amount of canalicular vacuoles, found in single hepatocytes that no longer maintain a polarized apical surface membrane ( 33 ). The above- described results are entirely consistent with the effects of cAMP presented here, involving a strong stimulation of apically directed lipid transport and a drastic increase in number and size of bile canalicular structures.…”

Section: Discussionmentioning

confidence: 99%

Sphingolipid Transport to the Apical Plasma Membrane Domain in Human Hepatoma Cells Is Controlled by PKC and PKA Activity: A Correlation with Cell Polarity in HepG2 Cells

Zegers

Hoekstra

1997

The Journal of Cell Biology

114

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The regulation of sphingolipid transport to the bile canalicular apical membrane in the well differentiated HepG2 hepatoma cells was studied. By employing fluorescent lipid analogs, trafficking in a transcytosis-dependent pathway and a transcytosis-independent (‘direct') route between the trans-Golgi network and the apical membrane were examined. The two lipid transport routes were shown to operate independently, and both were regulated by kinase activity. The kinase inhibitor staurosporine inhibited the direct lipid transport route but slightly stimulated the transcytosis-dependent route. The protein kinase C (PKC) activator phorbol-12 myristate-13 acetate (PMA) inhibited apical lipid transport via both transport routes, while a specific inhibitor of this kinase stimulated apical lipid transport. Activation of protein kinase A (PKA) had opposing effects, in that a stimulation of apical lipid transport via both transport routes was seen. Interestingly, the regulatory effects of either kinase activity in sphingolipid transport correlated with changes in cell polarity. Stimulation of PKC activity resulted in a disappearance of the bile canalicular structures, as evidenced by the redistribution of several apical markers upon PMA treatment, which was accompanied by an inhibition of apical sphingolipid transport. By contrast, activation of PKA resulted in an increase in the number and size of bile canaliculi and a concomitant enhancement of apical sphingolipid transport. Taken together, our data indicate that apical membrane-directed sphingolipid transport in HepG2 cells is regulated by kinases, which could play a role in the biogenesis of the apical plasma membrane domain.

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Thawed human hepatocytes in primary culture

et al. 1992

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Intracellular lumina and bile canaliculi in rat hepatocytes in vitro — a cytochemical study

Cited by 6 publications

References 9 publications

Mechanisms and functional features of polarized membrane traffic in epithelial and hepatic cells

Mechanisms and functional features of polarized membrane traffic in epithelial and hepatic cells

Sphingolipid Transport to the Apical Plasma Membrane Domain in Human Hepatoma Cells Is Controlled by PKC and PKA Activity: A Correlation with Cell Polarity in HepG2 Cells

Thawed human hepatocytes in primary culture

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