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Updated: Aug 1, 2025

Rapid Generation of Amyloid from Native Proteins In vitro
Published on: December 5, 2013
AL(light chain)-amyloidogenesis by mesangial cells involves active participation of lysosomes: An ultrastructural
Guillermo A Herrera1,2, Jiamin Teng3, Chun Zeng3
1University of South Alabama, USA.
Abstract:
Amyloid formation by cells is a stepwise process that occurs in macrophages and cells capable of transforming into a macrophage phenotype. One such cell is the mesangial cell in the kidney. It has been shown that mesangial cells are engaged in AL (light chain associated)- amyloidogenesis after transforming phenotypically from a smooth muscle to a macrophage phenotype. The actual process of amyloid fibril formation has not been dissected. This ultrastructural study which includes the examination of lysosomal gradient specimens addresses this issue by analyzing the sequence of events that takes place as fibrils are formed in endosomes and lysosomes. The findings indicate that fibrillogenesis begins in endosomes but is completed and most pronounced in the lysosomal compartment. As early as 10 min after incubation of human mesangial cells with AL-LCs, amyloid fibrils are formed in endosomes but mostly occurs in the mature lysosomal compartment. This is the first time that fibril formation is demonstrated experimentally occurring inside human mesangial cells and the entire sequence of events taking place is elucidated.
Insights
Kidney mesangial cells form amyloid fibrils within endosomes and lysosomes. This study reveals the complete sequence of amyloid fibril formation inside these specialized kidney cells.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Amyloid formation is a stepwise process observed in macrophages.
- Mesangial cells in the kidney can transform into macrophages and participate in amyloidogenesis.
- The precise mechanism of amyloid fibril formation within cells remains unclear.
Purpose of the Study:
- To dissect the ultrastructural sequence of amyloid fibril formation within human mesangial cells.
- To investigate the role of endosomes and lysosomes in AL-amyloidogenesis.
- To elucidate the cellular events during amyloid fibril assembly.
Main Methods:
- Ultrastructural examination of lysosomal gradient specimens from human mesangial cells.
- Incubation of human mesangial cells with AL-light chains (AL-LCs).
- Time-course analysis of amyloid fibril formation.
Main Results:
- Amyloid fibril formation initiates in endosomes.
- Fibrillogenesis is completed and most prominent within the lysosomal compartment.
- Amyloid fibrils were observed within 10 minutes of incubation in human mesangial cells.
Conclusions:
- This study provides the first experimental demonstration of amyloid fibril formation inside human mesangial cells.
- The complete sequence of AL-amyloidogenesis within these cells has been elucidated.
- Endosomes and lysosomes are critical compartments for amyloid fibril assembly in mesangial cells.
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