Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Intracellular accumulation of pIgA-R and regulators of transcytotic trafficking in cholestatic rat hepatocytes.

Authors: Larkin, JM  Coleman, H  Espinosa, A  Levenson, A  Park, MS  Woo, B  Zervoudakis, A  Tinh, V 
Citation: Larkin JM, etal., Hepatology 2003 Nov;38(5):1199-209.
Pubmed: (View Article at PubMed) PMID:14578858
DOI: Full-text: DOI:10.1053/jhep.2003.50419

Bile duct ligation (BDL) impairs basolateral-to-apical transcytosis in hepatocytes, causing accumulation of transcytotic carriers for the polymeric IgA receptor (pIgA-R) and redistribution of secretory component (SC) from bile to blood. To gain insight into the mechanisms regulating transcytosis and the pathophysiology of cholestasis, we investigated nascent protein trafficking in control and BDL livers using cell fractionation in the context of in vivo pulse-chase experiments and immunoblot analysis. Control and cholestatic hepatocytes trafficked [35S]-labeled serum proteins and the pIgA-R along the secretory pathway with identical kinetics. However, BDL impaired transcytosis, causing (1) accumulation of the pIgA-R, rab3D, rab11a, and other candidate regulators of apical-directed secretion in a crude vesicle carrier fraction (CVCF) enriched in transcytotic carriers; (2) slow delivery of [35S]-labeled SC to bile; and (3) paracellular reflux of SC from bile to blood. In conclusion, these data indicate that the secretory and transcytotic pathways remain polarized in cholestatic hepatocytes and suggest that the pIgA-R traffics through postendosomal rab3D-, rab11a-, and syntaxin 2-associated compartments, implicating these proteins in the regulation of transcytosis.


Gene Ontology Annotations
Objects Annotated

Additional Information

RGD Object Information
RGD ID: 1304451
Created: 2004-12-22
Species: All species
Last Modified: 2004-12-22
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.