Biology subjects

Sago, L.

Publications and source records attributed to Sago, L..

4 recordsLinked to original sources

bioRxiv2026

The actin-binding protein drebrin interacts with the respiratory syncytial virus matrix protein and promotes virus particle release.

Respiratory syncytial virus (RSV) is an enveloped virus that assembles and buds at the plasma membrane, producing filamentous infectious particles. Unlike many other enveloped viruses, a substantial fraction of RSV virions remains associated with the surface of infected cells, limiting our understanding of the membrane-scission mechanisms responsible for particle release. Here, we identified the actin-binding protein drebrin as a cellular interactor of the RSV matrix (M) protein, both in vitro and in infected cells. We demonstrated that RSV infection induces the relocalization of drebrin to actin-rich structures at the cell periphery associated with viral filaments. Using a Transwell-based assay to quantify infectious particles release without mechanically perturbing cells, we confirmed that RSV release is independent of the endosomal sorting complex required for transport (ESCRT) pathway and showed that drebrin depletion reduced RSV release, whereas drebrin overexpression enhanced it. Since drebrin depletion did not significantly affect overall infectious virus production, our results suggest that drebrin may act during the final step leading to membrane scission and RSV particle release. Finally, proteomics analysis identified Transmembrane 9 superfamily member 2 (TM9SF2) as a drebrin-associated protein specifically during infection. TM9SF2 depletion reduced RSV particle release and impaired the RSV-induced relocalization of drebrin to the plasma membrane. Together, these findings identify drebrin and TM9SF2 as host factors regulating RSV release and support a model in which TM9SF2 promotes the recruitment of drebrin to viral budding sites.

microbiology↗

bioRxiv2025

KIAA1217/SKT is a centrosomal protein that regulates ciliogenesis

Centrosomes organize the microtubule network along the cell cycle and drive cilia assembly in resting cells to allow sensory or motility functions. Defects in cilia formation underlie ciliopathies and skeletal disorders, but the molecular regulators that couple centrosomes to signaling and cytoskeletal networks remain incompletely defined. Through BioID screening for CYLD interactors, we identify KIAA1217/SKT as a centrosomal and microtubule plus-end protein that also associates with focal adhesions. KIAA1217 loss in RPE-1 cells impaired ciliogenesis, producing fewer and shorter cilia. Domain mapping revealed an N-terminal centrosomal targeting domain and an EB1-dependent targeting of KIAA1217 to microtubule tips via C-terminal SxIP motifs. Importantly, defects caused by loss of KIAA1217 or its paralog p140Cap were rescued by inhibiting actin polymerization or Src activity, indicating regulation of actin polymerization through Src family activity. Together, our findings establish KIAA1217 as a positive regulator of ciliogenesis that integrates Src-dependent signaling, centrosomal architecture, and actin remodeling and may open new research avenues to understand KIAA1217-associated pathologies as vertebrate malformation and epithelia-mesenchymal transition. Centrosome, Ciliogenesis, Actin, Src family signaling, KIAA217/SKT, p140Cap

cell biology↗

bioRxiv2025

NAP1 switches from an activator to a limiter of interferon induction by trapping TBK1 in condensates

TBK1 kinase is a central regulator of type I IFN production. Upon activation of the IFN-{beta} induction pathway, TBK1-adaptor proteins (NAP1, SINTBAD, TANK) form condensates with liquid properties. We showed that NAP1 condensates concentrate TBK1. Using NAP1KO cell lines, we discovered that NAP1 exerts a dual effect on TBK1 activity. Initially, NAP1 binds TBK1 and increases its activity, which enhances the activation of the IFN pathway. Then, phosphorylation of NAP1 by TBK1 induces the formation of NAP1 condensates. These condensates concentrate TBK1 and PP2A, a phosphatase known to dephosphorylate and consequently deactivate TBK1, thus limiting IFN induction. Additionally, in patients with lupus or interferonopathies, we identified NAP1 variants, unable to form condensates upon cell exposure to danger signals, which can only activate TBK1 without limiting its activity. This study reveals an original mode of regulating a signaling pathway by formation of condensates and provides a molecular explanation for certain interferonopathies.

immunology↗

bioRxiv2023

NatB-dependent acetylation protects procaspase-8 from UBR4-mediated degradation and is required for full induction of the extrinsic apoptosis pathway

N-terminal acetyltransferase B (NatB) is a major contributor to the N-terminal acetylome and is implicated in several key cellular processes including apoptosis and proteostasis. However, the molecular mechanisms linking NatB-mediated N-terminal acetylation to apoptosis and its relationship with protein homeostasis remain elusive. In this study, we generated mouse embryonic fibroblasts (MEFs) with an inactivated catalytic subunit of NatB (Naa20-/-) to investigate the impact of NatB deficiency on apoptosis regulation. Through quantitative N-terminomics, label-free quantification, and targeted proteomics, we demonstrated that NatB does not influence the proteostasis of all its substrates. Instead, our focus on putative NatB-dependent apoptotic factors revealed that NatB-mediated acetylation serves as a protective shield against UBR4 and UBR1 Arg/N-recognin-mediated degradation. Notably, Naa20-/- MEFs exhibited reduced responsiveness to extrinsic pro-apoptotic stimuli, a phenotype that was partially reversible upon UBR4 Arg/N-recognin silencing and consequent inhibition of procaspase-8 degradation. Collectively, our results shed light on how the interplay between NatB-mediated acetylation and the Arg/N-degron pathway impacts apoptosis regulation, providing new perspectives in the field including in therapeutic interventions.

biochemistry↗