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© The Rockefeller University Press, 0021-9525/2002/10/37 $5.00
The Journal of Cell Biology, Volume 159, Number 1, 37-44

MAL2, a novel raft protein of the MAL family, is an essential component of the machinery for transcytosis in hepatoma HepG2 cells

¹ Centro de Biología Molecular "Severo Ochoa", Centro Nacional de Biotecnología, Universidad Autónoma de Madrid and Consejo Superior de Investigaciones Científicas, Cantoblanco, 28049 Madrid, Spain
² Departamento de Immunología and Oncología, Centro Nacional de Biotecnología, Universidad Autónoma de Madrid and Consejo Superior de Investigaciones Científicas, Cantoblanco, 28049 Madrid, Spain
³ Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain, B-1200 Brussels, Belgium
⁴ Departamento de Endocrinología, Hospital de la Princesa, 28006 Madrid, Spain
⁵ Oncology Research Unit and the University of Sidney Department of Pediatrics and Child's Health, The Children's Hospital, Westmead, NSW, 2145, Australia

Address correspondence to Miguel A. Alonso, Centro de Biología Molecular "Severo Ochoa," Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain. Tel.: 34-91-397-8037. Fax: 34-91-397-8087. E-mail: maalonso{at}cbm.uam.es

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.

Key Words: hepatocytes; transcytosis; lipid rafts; MAL family; polarized transport

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