title: Differential effect of cross-linking the CD98 heavy chain on fusion and amino acid transport in the human placental trophoblast (BeWo) cell line.
abstract: CD98 (otherwise known as 4F2) is an integral membrane protein with multiple functions including amino acid transport, integrin activation, cell fusion and cell activation. The molecular mechanisms coordinating these multiple functions remain unclear. We have studied CD98 heavy chain (hc) function in a human placental trophoblast cell line (BeWo). We show that cross-linking of CD98hc by incubation of cells in the presence of functional monoclonal antibodies causes cellular re-distribution of the protein from the cytoplasm to the plasma membrane as measured by flow cytometry, western blotting and quantitative immuno-electron microscopy. The latter technique also indicated that CD98hc is trafficked between cell surface and cytoplasmic pools in vesicles. Increased cell surface CD98 correlates with increased cellular fusion in BeWo cells. In addition, we show reduced LAT 1 surface expression and neutral amino acid transport in the presence of the CD98 mabs. The results thus suggest that the function of CD98 in cell fusion is distinct from its role in cellular nutrient delivery.
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK. paoladalton@yahoo.co.uk
authors.forename: Paola
authors.initials: P
authors.lastname: Dalton
authors.forename: Helen C
authors.initials: HC
authors.lastname: Christian
authors.forename: Christopher W G
authors.initials: CW
authors.lastname: Redman
authors.forename: Ian L
authors.initials: IL
authors.lastname: Sargent
authors.forename: C A R
authors.initials: CA
authors.lastname: Boyd
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D026905:Amino Acid Transport Systems / Q000378:metabolism*; D026921:Amino Acid Transport Systems, Neutral / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000648:ultrastructure; D015153:Blotting, Western; D002459:Cell Fusion; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000648:ultrastructure; D010920:Placenta / Q000166:cytology / Q000502:physiology*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D027282:Fusion Regulatory Protein 1, Heavy Chain; C110810:LAT protein, human; D008565:Membrane Proteins