RRC ID 89960
Author Ghosh S, Martin E, Chen Y, Amiera N, Singh S, Low KE, Girardello R, Hübner B, Dittmar G, Ludwig A.
Title Bulk delivery of a preassembled apical surface initiates epithelial lumen formation.
Journal Nat Commun
Abstract During de novo lumenogenesis, epithelial cells establish luminal identity by directing apical cargo to an apical membrane initiation site (AMIS). Although this process has been widely studied, the mechanisms governing AMIS formation and its progression into a luminal precursor remain poorly understood. Here we combine quantitative light and electron microscopy with proximity proteomics to demonstrate that apical cargo is delivered to the AMIS in large apical precursor organelles, termed vacuolar apical compartments (VACs). VACs possess a microvilli-rich cortex and undergo exocytic fusion at the AMIS to generate a nascent lumen. Lumen initiation is tightly coordinated with the assembly and rearrangement of apical cell junctions and requires the Crumbs complex protein PatJ. Together, our results show that PatJ is a key structural determinant of the apical-lateral interface and indicate that VACs act as specialized transport organelles that deliver a preassembled apical surface to the AMIS, enabling rapid and efficient lumen initiation.
Volume 17(1)
Published 2026-8-7
DOI 10.1038/s41467-026-75503-w
PII 10.1038/s41467-026-75503-w
PMID 42702604
PMC PMC13547361
MeSH Animals Cell Membrane* / metabolism Cell Membrane* / ultrastructure Cell Polarity Dogs Epithelial Cells* / cytology Epithelial Cells* / metabolism Epithelial Cells* / ultrastructure Madin Darby Canine Kidney Cells Membrane Proteins / genetics Membrane Proteins / metabolism Vacuoles* / metabolism Vacuoles* / ultrastructure
Resource
Human and Animal Cells Rab3-KO MDCK-II(RCB5102) Rab11-KO MDCK-II(RCB5112) Rab25-KO MDCK-II(RCB5125) Rab35-KO MDCK-II(RCB5134)