Assembly of tight junction belts by surface condensation and actin elongation
Alf Honigmann, Daxiao Sun, Xueping Zhao, Tina Wiegand, Giacomo Bartolucci, Cecilie Martin-Lemaitre, Stephan Grill, Anthony Hyman, Christoph Weber
tight junctions, cell-cell contacts, actin
Tight junctions play an essential role in sealing tissues, by forming belts of adhesion strands around cellular perimeters. The formation of a tight junction occurs into two steps, initiation at cell-cell contacts, and elongation around the perimeter. Recent work has shown that nucleation is governed by condensation of scaffold proteins. However, the mechanisms by which condensates are spatially controlled to initiate at cell-cell contacts and elongate around cell perimeters remain unknown. Here, we combined cell biology, molecular reconstitution and thermodynamic modelling to show that belt formation is driven by a surface phase transition coupled to actin polymerization. Adhesion receptor oligomerization provides the signal for local surface condensation of ZO proteins. Surface condensates directly facilitate actin polymerization and filament bundling, which drives elongation of receptor-ZO-actin condensates into a junctional belt. We conclude that surface phase transitions provide a robust mechanism to locally control the position and shape of protein condensates.