Non-cell-autonomous removal of protein aggregates via trogocytosis
- 1Yale University
Abstract
Protein aggregate formation can cause cell damage and contribute to tissue pathologies including neurodegeneration. Protein aggregates are normally eliminated by cell-intrinsic mechanisms of lysosomal (autophagic) degradation. However, degradative capacity varies between cell types, raising the possibility that high-capacity cell types, such as macrophages, may contribute to aggregate disposal from the low-capacity cells. Here, we show that cellular protein aggregates are removed by macrophages via trogocytosis -- a partial engulfment of the target cells. Lysosomal stress upon protein aggregate accumulation promotes cell surface expression of the transmembrane isoform of the macrophage growth factor CSF1 (tmCSF1), which is detected by macrophages through the CSF1 receptor to drive trogocytosis. Insufficient or impaired degradation of protein aggregates in lysosomes results in their transport along microtubules to the plasma membrane where they physically associate with tmCSF1. This enables macrophages to specifically trogocytose protein aggregates. These findings reveal a protein homeostasis system that eliminates protein aggregates in a non-cell-autonomous manner.
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BibTeX
@misc{kimura2026noncellautonomous,
title = {{Non-cell-autonomous removal of protein aggregates via trogocytosis}},
author = {Y. Kimura and K. Sato and A. R. Chavan and W. Kasberg and M. Silva and W. Qiu and N. Iyer and M. Innerberger and I. Siwanowicz and S. D. Pope and A. Rangavajhula and G.-Q. Yao and K. Insogna and E. T. Trautman and C. K. Bleck and x. su and J. Lippincott-Schwartz and R. Medzhitov},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.13.758691},
url = {https://www.biorxiv.org/content/10.64898/2026.10.13.758691v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Non-cell-autonomous removal of protein aggregates via trogocytosis
AU - Y. Kimura
AU - K. Sato
AU - A. R. Chavan
AU - W. Kasberg
AU - M. Silva
AU - W. Qiu
AU - N. Iyer
AU - M. Innerberger
AU - I. Siwanowicz
AU - S. D. Pope
AU - A. Rangavajhula
AU - G.-Q. Yao
AU - K. Insogna
AU - E. T. Trautman
AU - C. K. Bleck
AU - x. su
AU - J. Lippincott-Schwartz
AU - R. Medzhitov
PY - 2026
DA - 2026/10/13
PB - bioRxiv
DO - 10.64898/2026.10.13.758691
UR - https://www.biorxiv.org/content/10.64898/2026.10.13.758691v1
AB - Protein aggregate formation can cause cell damage and contribute to tissue pathologies including neurodegeneration. Protein aggregates are normally eliminated by cell-intrinsic mechanisms of lysosomal (autophagic) degradation. However, degradative capacity varies between cell types, raising the possibility that high-capacity cell types, such as macrophages, may contribute to aggregate disposal from the low-capacity cells. Here, we show that cellular protein aggregates are removed by macrophages via trogocytosis -- a partial engulfment of the target cells. Lysosomal stress upon protein aggregate accumulation promotes cell surface expression of the transmembrane isoform of the macrophage growth factor CSF1 (tmCSF1), which is detected by macrophages through the CSF1 receptor to drive trogocytosis. Insufficient or impaired degradation of protein aggregates in lysosomes results in their transport along microtubules to the plasma membrane where they physically associate with tmCSF1. This enables macrophages to specifically trogocytose protein aggregates. These findings reveal a protein homeostasis system that eliminates protein aggregates in a non-cell-autonomous manner.
ER -