Organization and function of tension-dependent complexes at adherens junctions

Abstract

Adherens junctions provide attachments between neighboring epithelial cells and a physical link to the cytoskeleton, which enables them to sense and transmit forces and to initiate biomechanical signaling. Examination of the Ajuba LIM protein Jub in Drosophila embryos revealed that it is recruited to adherens junctions in tissues experiencing high levels of myosin activity, and that the pattern of Jub recruitment varies depending upon how tension is organized. In cells with high junctional myosin, Jub is recruited to puncta near intercellular vertices, which are distinct from Ena-containing puncta, but can overlap Vinc-containing puncta. We identify roles for Jub in modulating tension and cellular organization, which are shared with the cytohesinStep, and the cytohesin adapter Sstn, and show that Jub and Sstn together recruit Step to adherens junctions under tension. Our observations establish Jub as a reporter of tension experienced at adherens junctions, and identify distinct types of tension-dependent and tension-independent junctional complexes. They also identify a role for Jub in mediating a feedback loop that modulates the distribution of tension and cellular organization in epithelia.

TheDrosophilaAfadin and ZO-1 homologues Canoe and Polychaetoid act in parallel to maintain epithelial integrity when challenged by adherens junction remodeling

“…A different speculative possibility is that Afadin and ZO-1 proteins form part of a single large and multivalent protein complex, but recruit into this complex different, nonredundant partners, making loss of both more deleterious than loss of either one alone. Future work, including superresolution imaging of Pyd and Cno, and identification and functional analysis of different binding partners may help resolve these mechanistic questions, and also help define what other proteins act in parallel or together with them—one intriguing candidate is the mechanosensitive junctional protein Jub/Ajuba (Razzell et al , 2018; Rauskolb et al , 2019). Defining interacting partners and parallel mechanisms for maintaining epithelial integrity is an important future direction.…”

The Drosophila Afadin and ZO-1 homologs Canoe and Polychaetoid act in parallel to maintain epithelial integrity when challenged by adherens junction remodeling

“…A different speculative possibility is that Afadin and ZO-1 proteins form part of a single large and multivalent protein complex, but recruit into this complex different, nonredundant partners, making loss of both more deleterious than loss of either one alone. Future work, including super-resolution imaging of Pyd and Cno, and identification and functional analysis of different binding partners may help resolve these mechanistic questions, and also help define what other proteins act in parallel or together with them-one intriguing candidate is the mechanosensitive junctional protein Jub/Ajuba (Razzell et al, 2018;Rauskolb et al, 2019) Defining interacting partners and parallel mechanisms for maintaining epithelial integrity is an important future direction.…”

Planar Cell Polarity and E-Cadherin in Tissue-Scale Shape Changes in Drosophila Embryos

“…The Ajuba LIM protein (Jub), a force-sensitive protein, is enriched at the interface, and loss of Jub enhances dorsal closure defects in mutants defective for cell adhesion ( Razzell et al, 2018 ). This protein accumulates at adherens junctions under tension and acts as a critical component of a negative-feedback loop, which stabilizes and distributes tension at adherens junctions at the interface ( Rauskolb et al, 2019 ). These studies strongly suggest that adherens junctions have fundamental functions in adapting to mechanical forces and coordinate the tissue and cell interactions leading to morphogenesis.…”