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

Hutchinson, AT; Ramsland, PA; Jones, DR; Agostino, M; Lund, ME; Jennings, CV; Bockhorni, V; Yuriev, E; Edmundson, AB; Raison, RL

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

Hutchinson, AT Ramsland, PA Jones, DR Agostino, M Lund, ME

Jennings, CV Bockhorni, V Yuriev, E Edmundson, AB Raison, RL

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Publication Type:: Journal Article
Citation:: Journal of Immunology, 2010, 185 (7), pp. 4179 - 4188
Issue Date:: 2010-10-01

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Field	Value	Language
dc.contributor.author	Hutchinson, AT	en_US
dc.contributor.author	Ramsland, PA	en_US
dc.contributor.author	Jones, DR	en_US
dc.contributor.author	Agostino, M	en_US
dc.contributor.author	Lund, ME https://orcid.org/0000-0001-7360-5041	en_US
dc.contributor.author	Jennings, CV	en_US
dc.contributor.author	Bockhorni, V	en_US
dc.contributor.author	Yuriev, E	en_US
dc.contributor.author	Edmundson, AB	en_US
dc.contributor.author	Raison, RL	en_US
dc.date.issued	2010-10-01	en_US
dc.identifier.citation	Journal of Immunology, 2010, 185 (7), pp. 4179 - 4188	en_US
dc.identifier.issn	0022-1767	en_US
dc.identifier.uri	http://hdl.handle.net/10453/13740
dc.description.abstract	Free κ L chains (FκLCs) 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 FκLCs interact with membranes remains unresolved. In this study, we show that FκLCs associate with sphingomyelin on the plasma membrane of myeloma cells. Moreover, membrane-bound FκLCs are aggregated, suggesting that aggregation is required for intercalation with membranes. Finally, we propose a model where the binding of FκLCs with sphingomyelin on secretory vesicle membranes is stabilized by self-aggregation, with aggregated FκLCs 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.	en_US
dc.relation.ispartof	Journal of Immunology	en_US
dc.relation.isbasedon	10.4049/jimmunol.1001956	en_US
dc.subject.classification	Immunology	en_US
dc.subject.mesh	Plasma Cells	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	Cell Membrane	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Multiple Myeloma	en_US
dc.subject.mesh	Multiprotein Complexes	en_US
dc.subject.mesh	Sphingomyelins	en_US
dc.subject.mesh	Blotting, Western	en_US
dc.subject.mesh	Enzyme-Linked Immunosorbent Assay	en_US
dc.subject.mesh	Electrophoresis, Polyacrylamide Gel	en_US
dc.subject.mesh	Flow Cytometry	en_US
dc.subject.mesh	Cell Separation	en_US
dc.subject.mesh	Transfection	en_US
dc.subject.mesh	Receptor Aggregation	en_US
dc.subject.mesh	Immunoglobulin Light Chains	en_US
dc.title	Free ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form	en_US
dc.type	Journal Article
utslib.citation.volume	7	en_US
utslib.citation.volume	185	en_US
utslib.for	1107 Immunology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	7	en_US
pubs.publication-status	Published	en_US
pubs.volume	185	en_US

Abstract:

Free κ L chains (FκLCs) 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 FκLCs interact with membranes remains unresolved. In this study, we show that FκLCs associate with sphingomyelin on the plasma membrane of myeloma cells. Moreover, membrane-bound FκLCs are aggregated, suggesting that aggregation is required for intercalation with membranes. Finally, we propose a model where the binding of FκLCs with sphingomyelin on secretory vesicle membranes is stabilized by self-aggregation, with aggregated FκLCs 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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/13740