Proteostasis maintenance by macrophage trogocytosis

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B562
Abstract ID: 4183

Presenting Author:
Yoshitaka Kimura , Associate Research Scientist at Yale Sch. of Med.

Abstract:

Cells are frequently exposed to a wide variety of stresses that perturb cellular fitness. Stressed cells autonomously drive the defense mechanism to maintain their homeostasis, such as DNA repair program upon DNA damage and chaperone induction and protein degradation pathway upon protein misfolding. However, how cell-to-cell interaction contributes to the maintenance of cellular fitness has been elusive. Here, we show that macrophages interact with proteotoxically stressed cells and promote their proteostasis. Cells undergoing protein aggregate accumulation are detected by macrophages, and a part of their body is taken up via trogocytosis. In this process, protein aggregates in stressed cells are transferred to macrophages, leading to the reduction of protein aggregate load in stressed cells. Mechanistically, the macrophage detection and uptake of protein aggregates requires the stressed cells to express membrane-associated isoform of a macrophage growth factor CSF1 (mCSF1), which is upregulated by endoplasmic reticulum stress response pathways. The analysis of mCSF1-deficient mice in systemic proteotoxicity model reveals mCSF1 suppresses cellular damage in tissues, suggesting the trogocytosis-mediated removal of protein aggregates contributes to cellular homeostasis in vivo. These findings point to the fundamental cellular stress responses to induce full-blown proteostasis through the communication to immune cells in cooperation with autonomous responses.