Free ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form

Free ? L chains (F?LCs) are expressed on the surface of myeloma cells and are being assessed as a therapeutic target for the treatment of multiple myeloma. Despite its clinical potential, the mechanism by which F?LCs interact with membranes remains unresolved. In this study, we show that F?LCs assoc...

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Main Authors: Hutchinson, A., Ramsland, Paul, Jones, D., Agostino, Mark, Lund, M., Jennings, C., Bockhorni, V., Yuriev, E., Edmundson, A., Raison, R.
Format: Journal Article
Published: American Association of Immunologists 2010
Online Access:http://hdl.handle.net/20.500.11937/29383
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author Hutchinson, A.
Ramsland, Paul
Jones, D.
Agostino, Mark
Lund, M.
Jennings, C.
Bockhorni, V.
Yuriev, E.
Edmundson, A.
Raison, R.
author_facet Hutchinson, A.
Ramsland, Paul
Jones, D.
Agostino, Mark
Lund, M.
Jennings, C.
Bockhorni, V.
Yuriev, E.
Edmundson, A.
Raison, R.
author_sort Hutchinson, A.
building Curtin Institutional Repository
collection Online Access
description Free ? L chains (F?LCs) are expressed on the surface of myeloma cells and are being assessed as a therapeutic target for the treatment of multiple myeloma. Despite its clinical potential, the mechanism by which F?LCs interact with membranes remains unresolved. In this study, we show that F?LCs associate with sphingomyelin on the plasma membrane of myeloma cells. Moreover, membrane-bound F?LCs are aggregated, suggesting that aggregation is required for intercalation with membranes. Finally, we propose a model where the binding of F?LCs with sphingomyelin on secretory vesicle membranes is stabilized by self-aggregation, with aggregated F?LCs exposed on the plasma membrane after exocytosis. Although it is well known that protein aggregates bind membranes, this is only the second example of an aggregate being found on the surface of cells that also secrete the protein in its native form. We postulate that many other aggregation-prone proteins may associate with cell membranes by similar mechanisms. Copyright© 2010 by The American Association of Immunologists, Inc.
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spelling curtin-20.500.11937-293832017-09-13T15:22:41Z Free ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form Hutchinson, A. Ramsland, Paul Jones, D. Agostino, Mark Lund, M. Jennings, C. Bockhorni, V. Yuriev, E. Edmundson, A. Raison, R. Free ? L chains (F?LCs) are expressed on the surface of myeloma cells and are being assessed as a therapeutic target for the treatment of multiple myeloma. Despite its clinical potential, the mechanism by which F?LCs interact with membranes remains unresolved. In this study, we show that F?LCs associate with sphingomyelin on the plasma membrane of myeloma cells. Moreover, membrane-bound F?LCs are aggregated, suggesting that aggregation is required for intercalation with membranes. Finally, we propose a model where the binding of F?LCs with sphingomyelin on secretory vesicle membranes is stabilized by self-aggregation, with aggregated F?LCs exposed on the plasma membrane after exocytosis. Although it is well known that protein aggregates bind membranes, this is only the second example of an aggregate being found on the surface of cells that also secrete the protein in its native form. We postulate that many other aggregation-prone proteins may associate with cell membranes by similar mechanisms. Copyright© 2010 by The American Association of Immunologists, Inc. 2010 Journal Article http://hdl.handle.net/20.500.11937/29383 10.4049/jimmunol.1001956 American Association of Immunologists unknown
spellingShingle Hutchinson, A.
Ramsland, Paul
Jones, D.
Agostino, Mark
Lund, M.
Jennings, C.
Bockhorni, V.
Yuriev, E.
Edmundson, A.
Raison, R.
Free ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form
title Free ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form
title_full Free ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form
title_fullStr Free ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form
title_full_unstemmed Free ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form
title_short Free ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form
title_sort free ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form
url http://hdl.handle.net/20.500.11937/29383