Biology subjects

LEBRUN, M.

Publications and source records attributed to LEBRUN, M..

3 recordsLinked to original sources

bioRxiv2026

Two anchoring proteins control daughter apical complex assembly in Toxoplasma gondii

During Toxoplasma gondii division, the apical complex--comprising the conoid, apical polar ring (APR), and preconoidal rings--assembles with precise spatiotemporal coordination to form functional daughter buds. Despite their essential roles in invasion, motility, and division, the scaffolding proteins orchestrating this ordered assembly have remained largely unidentified. Here, we identify and characterize RCC1-2 and APR8 as essential factors directing distinct, sequential phases of daughter cell apical complex construction. Both proteins are recruited with precise spatial and temporal dynamics to the daughter buds, where they function as scaffolds rather than static structural components. APR8 transiently occupies the basal region of the APR specifically in early daughter cells. It is dispensable for conoid and PCR initiation, yet its loss causes APR collapse, abolishes SPMT anchoring, and eventually arrests conoid maturation. In contrast, RCC1-2 localizes beneath the APR basal layer and persists throughout daughter cell development, where it contributes to stabilizing the attachment of SPMTs to the APR. Notably, in situ cryo-electron tomography further reveals that the interspersed pillars bridging SPMTs ends to the APR fail to form properly in RCC1-2-depleted parasites. These findings map a hierarchical RCC1-2/APR8-dependent scaffolding process that advances our understanding of parasite replication.

microbiology↗

bioRxiv2025

An oncolytic herpesvirus expressing a CXCR4 antagonist interferes with Glioblastoma cells stemness features and migration.

Glioblastoma is one of the most aggressive brain tumors. Despite the standard therapy, the survival from diagnosis remains dramatically low, especially due to relapses. Considering their capacity to escape the tumor and to migrate to the subventricular zone through a CXCR4-dependant mechanism, Glioblastoma stem-like cells (GSCs) are considered as responsible for these relapses. CXCR4 regulates biological features associated with tumor progression, including self-renewal, migration and radio-resistance. Importantly, its expression correlates with severity and poor prognosis of several cancers including GBM. CXCR4/CXCL12 pathway appears therefore as an interesting potential therapeutic target. We have generated an oncolytic herpesvirus (oHSV) expressing HA-P2G, a mutated form of CXCL12 previously described as a CXCR4 competitive inhibitor. We demonstrate that in vitro, oHSV/P2G impairs human primary GSCs stemness markers expression, self-renewal and migration. In an orthotopic xenograft murine model, its injection within the tumor limits tumor growth and GSCs migration. The ability of P2G to interfere with major GSC features demonstrates the interest in considering oHSV/P2G as a promising new therapeutic approach for glioblastoma patients.

cancer biology↗

bioRxiv2022

An apical membrane complex controls rhoptry exocytosis and invasion in Toxoplasma

Apicomplexan parasites possess secretory organelles called rhoptries that undergo regulated exocytosis upon contact with the host. This process is essential for the parasitic lifestyle of these pathogens and relies on an exocytic machinery sharing structural features and molecular components with free-living ciliates. Here, we performed a Tetrahymena-based transcriptomic screen to uncover novel exocytic factors in Ciliata and Apicomplexa. We identified membrane-bound proteins, named CRMPs, forming part of a large complex essential for rhoptry secretion and invasion in Toxoplasma. In contrast to previously described rhoptry exocytic factors, TgCRMPs are not required for the assembly of the rhoptry secretion machinery and only transiently associated with the exocytic site - prior to invasion. CRMPs and their partners contain putative host cell-binding domains, and CRMPa shares similarity to GPCR proteins. We propose that the CRMP complex acts as host-molecular sensor to ensure that rhoptry exocytosis occurs when the parasite contacts the host cell.

cell biology↗