Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 455K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by de Marco, M. C. Articles by Alonso, M. A. Search for Related Content PubMed PubMed Citation Articles by de Marco, M. C. Articles by Alonso, M. A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene OMIM Protein UniGene Substance via MeSH Medline Plus Health Information Liver Cancer Social Bookmarking                      What's this?

© 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

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Snooks, M. J., Bhat, P., Mackenzie, J., Counihan, N. A., Vaughan, N., Anderson, D. A. (2008). Vectorial Entry and Release of Hepatitis A Virus in Polarized Human Hepatocytes. J. Virol. 82: 8733-8742 [Abstract] [Full Text]  
• Spaderna, S., Schmalhofer, O., Wahlbuhl, M., Dimmler, A., Bauer, K., Sultan, A., Hlubek, F., Jung, A., Strand, D., Eger, A., Kirchner, T., Behrens, J., Brabletz, T. (2008). The Transcriptional Repressor ZEB1 Promotes Metastasis and Loss of Cell Polarity in Cancer. Cancer Res. 68: 537-544 [Abstract] [Full Text]  
• Kamsteeg, E.-J., Duffield, A. S., Konings, I. B. M., Spencer, J., Pagel, P., Deen, P. M. T., Caplan, M. J. (2007). MAL decreases the internalization of the aquaporin-2 water channel. Proc. Natl. Acad. Sci. USA 104: 16696-16701 [Abstract] [Full Text]  
• Ramnarayanan, S. P., Cheng, C. A., Bastaki, M., Tuma, P. L. (2007). Exogenous MAL Reroutes Selected Hepatic Apical Proteins into the Direct Pathway in WIF-B Cells. Mol. Biol. Cell 18: 2707-2715 [Abstract] [Full Text]  
• Navarro-Lerida, I., Martinez-Moreno, M., Ventoso, I., Alvarez-Barrientos, A., Rodriguez-Crespo, I. (2007). Binding of CAP70 to Inducible Nitric Oxide Synthase and Implications for the Vectorial Release of Nitric Oxide in Polarized Cells. Mol. Biol. Cell 18: 2768-2777 [Abstract] [Full Text]  
• Leyt, J., Melamed-Book, N., Vaerman, J.-P., Cohen, S., Weiss, A. M., Aroeti, B. (2007). Cholesterol-sensitive Modulation of Transcytosis. Mol. Biol. Cell 18: 2057-2071 [Abstract] [Full Text]  
• Rohan, S., Tu, J. J., Kao, J., Mukherjee, P., Campagne, F., Zhou, X. K., Hyjek, E., Alonso, M. A., Chen, Y.-T. (2006). Gene Expression Profiling Separates Chromophobe Renal Cell Carcinoma from Oncocytoma and Identifies Vesicular Transport and Cell Junction Proteins as Differentially Expressed Genes. Clin. Cancer Res. 12: 6937-6945 [Abstract] [Full Text]  
• Manninen, A., Verkade, P., Le Lay, S., Torkko, J., Kasper, M., Fullekrug, J., Simons, K. (2005). Caveolin-1 Is Not Essential for Biosynthetic Apical Membrane Transport. Mol. Cell. Biol. 25: 10087-10096 [Abstract] [Full Text]  
• Tiacci, E., Orvietani, P.-L., Bigerna, B., Pucciarini, A., Corthals, G. L., Pettirossi, V., Martelli, M. P., Liso, A., Benedetti, R., Pacini, R., Bolli, N., Pileri, S., Pulford, K., Gambacorta, M., Carbone, A., Pasquarello, C., Scherl, A., Robertson, H., Sciurpi, M. T., Alunni-Bistocchi, G., Binaglia, L., Byrne, J. A., Falini, B. (2005). Tumor protein D52 (TPD52): a novel B-cell/plasma-cell molecule with unique expression pattern and Ca2+-dependent association with annexin VI. Blood 105: 2812-2820 [Abstract] [Full Text]  
• Schuck, S., Simons, K. (2004). Polarized sorting in epithelial cells: raft clustering and the biogenesis of the apical membrane. J. Cell Sci. 117: 5955-5964 [Abstract] [Full Text]  
• Llorente, A., de Marco, M. C., Alonso, M. A. (2004). Caveolin-1 and MAL are located on prostasomes secreted by the prostate cancer PC-3 cell line. J. Cell Sci. 117: 5343-5351 [Abstract] [Full Text]  
• Thomas, D. D. H., Weng, N., Groblewski, G. E. (2004). Secretagogue-induced translocation of CRHSP-28 within an early apical endosomal compartment in acinar cells. Am. J. Physiol. Gastrointest. Liver Physiol. 287: G253-G263 [Abstract] [Full Text]  
• Hoang, C. D., D'Cunha, J., Kratzke, M. G., Casmey, C. E., Frizelle, S. P., Maddaus, M. A., Kratzke, R. A. (2004). Gene Expression Profiling Identifies Matriptase Overexpression in Malignant Mesothelioma. Chest 125: 1843-1852 [Abstract] [Full Text]  
• Hoekstra, D., Tyteca, D., van IJzendoorn, S. C. D. (2004). The subapical compartment: a traffic center in membrane polarity development. J. Cell Sci. 117: 2183-2192 [Abstract] [Full Text]  
• Marazuela, M., Acevedo, A., Garcia-Lopez, M. A., Adrados, M., de Marco, M. C., Alonso, M. A. (2004). Expression of MAL2, an Integral Protein Component of the Machinery for Basolateral-to-Apical Transcytosis, in Human Epithelia. J. Histochem. Cytochem. 52: 243-252 [Abstract] [Full Text]  
• Marazuela, M., Martin-Belmonte, F., Garcia-Lopez, M. A., Aranda, J. F., de Marco, M. C., Alonso, M. A. (2004). Expression and Distribution of MAL2, an Essential Element of the Machinery for Basolateral-to-Apical Transcytosis, in Human Thyroid Epithelial Cells. Endocrinology 145: 1011-1016 [Abstract] [Full Text]  
• Kaspar, K. M., Thomas, D. D. H., Taft, W. B., Takeshita, E., Weng, N., Groblewski, G. E. (2003). CaM kinase II regulation of CRHSP-28 phosphorylation in cultured mucosal T84 cells. Am. J. Physiol. Gastrointest. Liver Physiol. 285: G1300-G1309 [Abstract] [Full Text]  
• Martin-Belmonte, F., Martinez-Menarguez, J. A., Aranda, J. F., Ballesta, J., de Marco, M. C., Alonso, M. A. (2003). MAL regulates clathrin-mediated endocytosis at the apical surface of Madin-Darby canine kidney cells. JCB 163: 155-164 [Abstract] [Full Text]  
• TUMA, P. L., HUBBARD, A. L. (2003). Transcytosis: Crossing Cellular Barriers. Physiol. Rev. 83: 871-932 [Abstract] [Full Text]  
• Nyasae, L. K., Hubbard, A. L., Tuma, P. L. (2003). Transcytotic Efflux from Early Endosomes Is Dependent on Cholesterol and Glycosphingolipids in Polarized Hepatic Cells. Mol. Biol. Cell 14: 2689-2705 [Abstract] [Full Text]  
• Marazuela, M., Acevedo, A., Adrados, M., Garcia-Lopez, M. A., Alonso, M. A. (2003). Expression of MAL, an Integral Protein Component of the Machinery for Raft-mediated Apical Transport, in Human Epithelia. J. Histochem. Cytochem. 51: 665-674 [Abstract] [Full Text]  
• Hoekstra, D., Maier, O., van der Wouden, J. M., Slimane, T. A., van IJzendoorn, S. C. D. (2003). Membrane dynamics and cell polarity: the role of sphingolipids. J. Lipid Res. 44: 869-877 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents