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bioRxiv · 10.64898/2026.01.13.699385

A PKD-caveolin axis drives secretory carrier biogenesis at the TGN

Wakana, Y.·Sugiura, H.·Fujii, M.·Terashima, Y.·Takagi, Y.·Angulo-Capel, J.·Tagaya, M.·Inoue, H.·Arasaki, K.·Campelo, F.
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Abstract

Constitutive secretion from the trans-Golgi network (TGN) to the cell surface proceeds via carriers thought to form without a canonical cytoplasmic coat, yet how these carriers are generated remains poorly understood. Here, we identify a distinct population of TGN-to-cell surface carriers transporting influenza hemagglutinin (HA) and uncover a coat-like mechanism underlying their formation. HA carrier biogenesis requires non-vesicular lipid transfer at endoplasmic reticulum (ER)-Golgi membrane contact sites (MCSs) and protein kinase D (PKD) activity. We show that caveolin promotes membrane budding by assembling into cholesterol- and PKD-associated oligomers that act as a membrane-embedded, coat-like scaffold at lipid nanodomain-enriched TGN subdomains. These findings establish caveolin as a structural and regulatory component of TGN export and support a model in which a PKD-caveolin axis couples ER-Golgi lipid transfer to cargo sorting, membrane remodeling and fission during secretory carrier biogenesis.

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Wakana, Y., Sugiura, H., Fujii, M., Terashima, Y., Takagi, Y., Angulo-Capel, J., Tagaya, M., Inoue, H., Arasaki, K., Campelo, F.. 2026-01-14. A PKD-caveolin axis drives secretory carrier biogenesis at the TGN. https://doi.org/10.64898/2026.01.13.699385

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