Rab11a and Myosin Vb Are Required for Bile Canalicular Formation in WIF-B9 Cells

Hepatocytes polarize by forming functionally distinct sinusoidal (basolateral) and canalicular (apical) plasma membrane domains. Two distinct routes are used for delivery of membrane proteins to the canaliculus. Proteins having glycosylphosphatidylinositol anchors or single transmembrane domains are...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-10, Vol.102 (42), p.15087-15092
Main Authors: Yoshiyuki Wakabayashi, Dutt, Parmesh, Lippincott-Schwartz, Jennifer, Arias, Irwin M.
Format: Article
Language:English
Subjects:
Adenoviruses
Animals
ATP binding cassette transporters
Bile
Bile Canaliculi - cytology
Bile Canaliculi - growth & development
Bile Canaliculi - metabolism
Biological Sciences
Biological Transport - physiology
Cell culture techniques
Cell Line
Cell lines
Cell Membrane - chemistry
Cell Membrane - metabolism
Cell membranes
Cell Polarity
Cellular biology
Endosomes
Epithelial cells
Epithelial Cells - cytology
Epithelial Cells - metabolism
Hepatocytes
Hepatocytes - cytology
Hepatocytes - metabolism
Humans
Intracellular Membranes - chemistry
Intracellular Membranes - metabolism
Membrane proteins
Membranes
Myosin Heavy Chains - genetics
Myosin Heavy Chains - metabolism
Myosin Type V - genetics
Myosin Type V - metabolism
Myosins - genetics
Myosins - metabolism
P branes
Protein Isoforms - genetics
Protein Isoforms - metabolism
Proteins
rab GTP-Binding Proteins - genetics
rab GTP-Binding Proteins - metabolism
Rats
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
RNA Interference
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Summary:Hepatocytes polarize by forming functionally distinct sinusoidal (basolateral) and canalicular (apical) plasma membrane domains. Two distinct routes are used for delivery of membrane proteins to the canaliculus. Proteins having glycosylphosphatidylinositol anchors or single transmembrane domains are targeted to the sinusoidal plasma membrane from where they transcytose to the canalicular domain. In contrast apical ATP-binding-cassette (ABC) transporters, which are required for energy-dependent biliary secretion of bile acids (ABCB11), phospholipids (ABCB4), and nonbile acid organic anions (ABCC2), lack initial residence in the basolateral plasma membrane and traffic directly from Golgi membranes to the canalicular membrane. While investigating mechanisms of apical targeting in WIF-B9 cells, a polarized hepatic epithelial cell line, we observed that rab11a is required for canalicular formation. Knockdown of rab11a or overexpression of the rab11a-GDP locked form prevented canalicular formation as did overexpression of the myosin Vb motorless tail domain. In WIF-B9 cells, which lack bile canaliculi, apical ABC transporters colocalized with transcytotic membrane proteins in rab11a-containing endosomes and, unlike the transcytotic markers, did not distribute to the plasma membrane. We propose that polarization of hepatocytes (i.e., canalicular biogenesis) requires recruitment of rab11a and myosin Vb to intracellular membranes that contain apical ABC transporters and transcytotic markers, permitting their targeting to the plasma membrane. In this model, polarization is initiated upon delivery of rab11a-myosin Vb-containing membranes to the surface, which causes plasma membrane at the site of delivery to differentiate into apical domain (bile canaliculus).
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0503702102