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Abstract: TH-OR055

Sortilin-Related Receptor (SORL1) Mediates Glomerulopathic Light Chain Interactions with Mesangial Cells (MCs)

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Herrera, Guillermo A., Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States
  • Teng, Jiamin, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States
  • Shen, Xinggui, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States
  • Zeng, Chun, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States
  • Turbat-Herrera, Elba A., Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States
Background

It has been proven that glomerulopathic (G), but not tubulopathic (T) light chains (LCs) interact with mesangial cells (MCs) using a receptor membrane. Both light chain deposition disease (LCDD) and amyloid- producing (AL) LCs use the same receptor but lead to divergent downstream mesangial cell/matrix alterations. Tubulopathic LCs do not interact with MCs.

Methods

Three AL, two LCDD and one tubulopathic-LCs (10 ug/ml) were incubated with MCs for 30 minutes, cross-linked using DSTTP and subsequently, SPS-PAGE gels were run to identify bands. Bands above 70kD were cut and analyzed using mass spectroscopy (MS). Proteins obtained from various LCs cross linked to MCs were compared to identify receptors shared by the GLCs. TLC was used as a control. Fluorescein-labeled antibody to the SORL1 protein receptor and a second Texas red labeled antibody for the GLCs were used to evaluate for colocalization.

Results

Several transient MC receptors were shared by the 5 GLCs including: G-protein coupled, ligand-gated ion channel/transient receptor potential cation channel, subfamily M, and extracellular matrix linker protein receptor/cell adhesion-molecule extracellular matrix glycoprotein receptors. The one unique membrane receptor shared by the 5 GLCs was SORL1 located on chromosome 11, a lysosomal sorting receptor engaged in directing internalized proteins to the endolysosomal system and participating in microvesicular protein movement inside MCs. SORL1 was colocalized with both AL and LCDD light chains using double fluorescence labeling techniques. No localization was noted with TLC.

Conclusion

SORL1 (238 kD mw) was expressed when GLCs interact with MCs and not when TLCs were incubated with MCs or when MCs were incubated without LCs. Engagement of this receptor serves to direct GLCs, depending on their physicochemical characteristics, to various intracellular compartments where crucial pathogenetic events occur. SORL1 had not been previously identified as a MC receptor but it had been found to be present in the kidneys with no specific localization yet defined prior to this study. SORL1 was colocalized with LCDD and AL-LCs at the cell surfaces and inside MCs. There was no colocalization with TLC.