MAL2, a novel raft protein of the MAL family, is an essential component of the machinery for transcytosis in hepatoma HepG2 cells
Open Access
- 7 October 2002
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 159 (1), 37-44
- https://doi.org/10.1083/jcb.200206033
Abstract
Transcytosis is used alone (e.g., hepatoma HepG2 cells) or in combination with a direct pathway from the Golgi (e.g., epithelial MDCK cells) as an indirect route for targeting proteins to the apical surface. The raft-associated MAL protein is an essential element of the machinery for the direct route in MDCK cells. Herein, we present the functional characterization of MAL2, a member of the MAL protein family, in polarized HepG2 cells. MAL2 resided selectively in rafts and is predominantly distributed in a compartment localized beneath the subapical F-actin cytoskeleton. MAL2 greatly colocalized in subapical endosome structures with transcytosing molecules en route to the apical surface. Depletion of endogenous MAL2 drastically blocked transcytotic transport of exogenous polymeric immunoglobulin receptor and endogenous glycosylphosphatidylinositol-anchored protein CD59 to the apical membrane. MAL2 depletion did not affect the internalization of these molecules but produced their accumulation in perinuclear endosome elements that were accessible to transferrin. Normal transcytosis persisted in cells that expressed exogenous MAL2 designed to resist the depletion treatment. MAL2 is therefore essential for transcytosis in HepG2 cells.Keywords
This publication has 20 references indexed in Scilit:
- Absence of Direct Delivery for Single Transmembrane Apical Proteins or Their “Secretory” Forms in Polarized Hepatic CellsMolecular Biology of the Cell, 2002
- MAL Mediates Apical Transport of Secretory Proteins in Polarized Epithelial Madin-Darby Canine Kidney CellsJournal of Biological Chemistry, 2001
- Identification of MAL2, a Novel Member of the MAL Proteolipid Family, Though Interactions with TPD52-like Proteins in the Yeast Two-Hybrid SystemGenomics, 2001
- Actin Filaments and Microtubules are Involved in Different Membrane Traffic Pathways That Transport Sphingolipids to the Apical Surface of Polarized HepG2 CellsMolecular Biology of the Cell, 1998
- Structural and Biochemical Similarities Reveal a Family of Proteins Related to the MAL Proteolipid, a Component of Detergent-Insoluble Membrane MicrodomainsBiochemical and Biophysical Research Communications, 1997
- Receptor-mediated transcytosis of IgA in MDCK cells is via apical recycling endosomes.The Journal of cell biology, 1994
- 5'nucleotidase is sorted to the apical domain of hepatocytes via an indirect route [published erratum appears in J Cell Biol 1993 Nov;123(3):following 767]The Journal of cell biology, 1992
- Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surfaceCell, 1992
- Polarized sorting in epitheliaCell, 1990
- Polymeric immunoglobulin receptor expressed in MDCK cells transcytoses IgACell, 1986