The MAL Proteolipid Is Necessary for Normal Apical Transport and Accurate Sorting of the Influenza Virus Hemagglutinin in Madin-Darby Canine Kidney Cells

doi:10.1083/jcb.145.1.141

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© The Rockefeller University Press, 0021-9525/1999//141 $5.00
The Journal of Cell Biology, Volume 145, Number 1, , 1999 141-151

Regular Articles

The MAL Proteolipid Is Necessary for Normal Apical Transport and Accurate Sorting of the Influenza Virus Hemagglutinin in Madin-Darby Canine Kidney Cells

Rosa Puertollano^*, Fernando Martín-Belmonte^*, Jaime Millán^*, María del Carmen de Marco^*, Juan P. Albar, Leonor Kremer, and Miguel A. Alonso^*

^* Centro de Biología Molecular "Severo Ochoa," Universidad Autónoma de Madrid and Consejo Superior de Investigaciones Científicas, and Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Cantoblanco, 28049-Madrid, Spain

The MAL (MAL/VIP17) proteolipid is a nonglycosylated integralmembrane protein expressed in a restricted pattern of celltypes, including T lymphocytes, myelin-forming cells, and polarizedepithelial cells. Transport of the influenza virus hemagglutinin (HA) to the apical surface of epithelial Madin-Darby caninekidney (MDCK) cells appears to be mediated by a pathway involvingglycolipid- and cholesterol- enriched membranes (GEMs). In MDCKcells, MAL has been proposed previously as being an elementof the protein machinery for the GEM-dependent apical transportpathway. Using an antisense oligonucleotide-based strategy anda newly generated monoclonal antibody to canine MAL, hereinwe have approached the effect of MAL depletion on HA transportin MDCK cells. We have found that MAL depletion diminishes the presence of HA in GEMs, reduces the rate of HA transportto the cell surface, inhibits the delivery of HA to the apicalsurface, and produces partial missorting of HA to the basolateralmembrane. These effects were corrected by ectopic expressionof MAL in MDCK cells whose endogenous MAL protein was depleted. Our results indicate that MAL is necessary for both normalapical transport and accurate sorting of HA.

Key Words: apical transport • glycolipid-enriched membranes • sorting • Madin-Darby canine kidney cells • proteolipids

Abbreviations used in this paper: d, dog; GEM, glycolipid- and cholesterol-enriched membrane; h, human; HA, hemagglutinin; MDCK, Madin-Darby canine kidney; sulfo-NHS-biotin, sulfo-N-hydroxyl-succinimido-biotin.

R. Puertollano and F. Martín-Belmonte are recipientsof predoctoral fellowships from the Comunidad de Madrid. J.Millán and M. de Marco are supported by predoctoralfellowships from the Ministerio de Educación y Cultura.This work was supported by grants from the DirecciónGeneral de Enseñanza Superior (PM96-0004) and the Comunidadde Madrid (08.3/ 0020/1998). The Department of Immunology andOncology is funded and supported by the Consejo Superior deInvestigaciones Científicas and Pharmacia & Upjohn.An institutional grant from the Fundación RamónAreces to Centro de Biología Molecular "Severo Ochoa"is also acknowledged.

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