A conserved GTPase complex gates exocytosis for defence and parasitism across alveolates.

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.