FYCO1 regulates accumulation of post-mitotic midbodies by mediating LC3-dependent midbody degradation

Abstract

The post-mitotic midbody (MB) is a remnant of cytokinesis that can be asymmetrically inherited by one of the daughter cells following cytokinesis. Until recently, the MB was thought to be degraded immediately following cytokinesis. However, recent evidence suggests that the MB is a protein-rich organelle that accumulates in stem cell and cancer cell populations, indicating that it may have post-mitotic functions. Here, we investigate the role of FYCO1, an LC3-binding protein (herein, LC3 refers to MAP1LC3B), and its function in regulating the degradation of post-mitotic MBs. We show that FYCO1 is responsible for formation of LC3-containing membrane around the post-mitotic MB and that FYCO1 knockdown increases MB accumulation. Although MBs accumulate in the stem-cell-like population of squamous cell carcinomas, FYCO1 depletion does not affect the clonogenicity of these cells. Instead, MB accumulation leads to an increase in anchorage-independent growth and invadopodia formation in HeLa cells and squamous carcinoma cells. Collectively, our data suggest that FYCO1 regulates MB degradation, and we present the first evidence that cancer invasiveness is a feature that can be modulated by the accumulation of MBs in cancer stem cells.This article has an associated First Person interview with the first author of the paper.

FYCO1 mediates clearance of α‐synuclein aggregates through a Rab7‐dependent mechanism

“…4, Dinter et al 2016). Accordingly, Dionne et al (2017) saw no major defect in baseline autophagic flux in HeLa cells with FYCO knockdown.…”

“…; Dionne et al . ). Indeed, rare FYCO1 variants some of which contain missense mutations in the LIR domain have recently been associated with inclusion body myositis (Güttsches et al .…”

“…Yet, induction of transport towards the cell periphery is not the only effect of FYCO1. FYCO1 was recently shown to contribute to the maturation of autophagosomes and phagophores through its LIR domain (Ma et al 2014;Olsvik et al 2015;Dionne et al 2017). Indeed, rare FYCO1 variants some of which contain missense mutations in the LIR domain have recently been associated with inclusion body myositis (G€ uttsches et al 2017) a disease characterized by accumulation of protein aggregates and suspected impaired autophagic degradation.…”

Cytokinetic furrowing and abscission dynamics during brain development revealed by live imaging

“…Post-abscission midbody remnants (MBRs) have been shown to adhere to plasma membranes of daughter or neighbor cells, and may influence cell polarity or proliferation (22,24,32,33). We wanted to ask whether MBRs of cortical NSCs remain on the apical membrane after abscission, and whether this changes across development.…”

Suppression of autophagy during mitosis via CUL4-RING ubiquitin ligases-mediated WIPI2 polyubiquitination and proteasomal degradation

“…Under starvation condition, autophagy has been shown to be required for cell cycle progression and for maintenance of genome stability [15]. Moreover, autophagy has been revealed to be required for midbody ring digestion during the cytokinesis phase to ensure successful separation of the two daughter cells [16][17][18][19][20]. On the other hand, it remains unclear or controversial whether and how cell cycle regulates autophagy.…”