Year: 2026
Type: article
Abstract: Regulated protein secretion is a fundamental process by which eukaryotic cells respond to and interact with their dynamic environments, yet its mechanism outside metazoans remains largely unknown. Here we uncover an atypical small GTPase complex (Nd-GTPase–Nd9–NdP1) conserved across the Alveolata—a major eukaryotic clade encompassing ciliates and apicomplexan parasites—that gates organelle exocytosis for diverse functions ranging from cellular defence to host invasion. Using Tetrahymena thermophila and Toxoplasma gondii as comparative models, we combine functional genetics, cryo-electron tomography and integrative structural modelling to show that this complex maintains the organelle secretory apparatus in a pre-secretion state and permits activation upon stimulation. Comparative analysis further reveals that apicomplexan parasites rely on an apical vesicle to tighten control over secretion. These findings define a unifying principle of gated alveolate exocytosis, illustrating how evolution remodels an ancient secretion system to meet specialized cellular demands, and underlie key mechanisms of parasite virulence. A GTPase complex conserved across alveolates gates exocytosis in the parasite Toxoplasma and the ciliate Tetrahymena. In Toxoplasma, an added apical vesicle tightens control over rhoptry secretion, a process critical to host cell invasion.
Source: Nature Microbiology
Institutions: Centre National de la Recherche Scientifique, Inserm, Université de Montpellier, Laboratory of Pathogens and Host Immunity, University of Pennsylvania, Institut Agro Montpellier, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Institut des Sciences des Plantes de Montpellier, University of Victoria
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: Pennsylvania Department of Health, University of Pennsylvania, Aarhus Universitet, Alliance Française contre les Maladies Parasitaires, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Université de Genève, Université de Montpellier, National Institutes of Health, National Institute of General Medical Sciences, Army Research Office
OpenAlex ID: W7216346150