Free Ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form.
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.
Hutchinson
Andrew T
AT
Department of Medical and Molecular Biosciences, University of Technology Sydney, Ultimo, New South Wales, Australia. andrew.hutchinson@uts.edu.au
Ramsland
Paul A
PA
Jones
Darren R
DR
Agostino
Mark
M
Lund
Maria E
ME
Jennings
Cameron V
CV
Bockhorni
Vanessa
V
Yuriev
Elizabeth
E
Edmundson
Allen B
AB
Raison
Robert L
RL
D015153:Blotting, Western; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D046912:Multiprotein Complexes; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D011940:Receptor Aggregation / Q000502:physiology; D013109:Sphingomyelins / Q000378:metabolism*; D014162:Transfection
D007147:Immunoglobulin Light Chains; D046912:Multiprotein Complexes; D013109:Sphingomyelins