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Removal of cellular protrusions - PubMed

Review

Removal of cellular protrusions

Mayu Inaba et al. Semin Cell Dev Biol. 2022 Sep.

Abstract

Cell-cell communications are central to a variety of physiological and pathological processes in multicellular organisms. Cells often rely on cellular protrusions to communicate with one another, which enable highly selective and efficient signaling within complex tissues. Owing to significant improvements in imaging techniques, identification of signaling protrusions has increased in recent years. These protrusions are structurally specialized for signaling and facilitate interactions between cells. Therefore, physical regulation of these structures must be key for the appropriate strength and pattern of signaling outcomes. However, the typical approaches for understanding signaling regulation tend to focus solely on changes in signaling molecules, such as gene expression, protein-protein interaction, and degradation. In this short review, we summarize the studies proposing the removal of different types of signaling protrusions-including cilia, neurites, MT (microtubule based)-nanotubes and microvilli-and discuss their mechanisms and significance in signaling regulation.

Keywords: Cilia; Ectocytosis; Microtubule-based (MT)-nanotubes; Neurite pruning; Phagocytosis; Signaling protrusion; Trogocytosis.

Copyright © 2022 Elsevier Ltd. All rights reserved.

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Conflict of interest statement

Competing Financial Interest Statement

The authors have no competing financial interests to declare.

Figures

Figure 1.
Figure 1.. Vesicles derived from different portions of cilia.

Large EVs (ectosomes) are typically shed from the tip region of cilia and phagocytosed, while small EVs (exosomes) are released from the base of cilia. Small EVs often exhibit bioactivity.

Figure 2.
Figure 2.. Shedding of cilia regulates turnover of signaling molecules.

A) Shedding of outer segments of photoreceptors (purple cell). Outer segment discs contain rhodopsin, which belongs to the GPCR superfamily. Rhodopsins undergo both a conformational change (becoming opsins) and activation of the G protein upon receiving a photon, and need to be renewed/replaced daily. Part of the outer segment disk containing used opsins is shed, phagocytosed by neighboring retinal pigment epithelium (RPE) cells, transformed back to rhodopsins, and then transported into photoreceptor cells. B) GPCRs (receptors) localize to cilia and accumulates in the tip portion. Upon stimulation by the hedgehog ligand, GPCRs that fail to be retrieved from the tip are removed by ectocytosis.

Figure 3.
Figure 3.. Tkv removal from MT-nanotubes is required for signal adjustment

(Left) Microtubule (MT)-nanotube appears on the Drosophila GSC and promotes the reception of Dpp ligand secreted from the niche, a cluster of hub cells. (Right) Shedding of MT-nanotube membrane and potential engulfment by hub cells. Vesicles taken up are fused to lysosomes in hub cells and ultimately degraded, resulting in attenuation of the signal.

Figure 4.
Figure 4.. Phagocytes can bite off protrusions (Trogocytosis).

(Left) PtdSer normally localizes to the inner leaflet of the plasma membranes via the function of flippase. Scramblase is activated by Ca2+ and scrambles PtdSer localization. (Middle) Externally localized PtdSer is recognized by phagocytic receptors, and these receptors recruit actomyosin to the phagocytic cups. Phagocytic cups generate constriction forces to “bite” up the tip of the protrusion (Right). Protrusions are cell-autonomously shed via activating ESCRT. These mechanisms were both reported in the engulfment of photoreceptor outer segment, and thus may occur simultaneously (see text).

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