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A screen for adherens junction proteins regulating collective cell migration and testis morphogenesis reveals important roles for the Rab GAP RN-tre and the kinase Par-1.

Created on 30 Jul 2026

Authors

Sarah E Clark, Siobhan C Morris, Joseph B Dordor, Lawrencia S Amo, Renick Wiltshire, Taino Encarnacion, Maik C Bischoff, Mark Peifer

Published in

Molecular biology of the cell. Pages mbcE26050234. Jul 29, 2026. Epub Jul 29, 2026.

Abstract

Animal tissues have diverse architectures and cell behaviors across the epithelial-mesenchymal spectrum. Cell adhesion mediated by classical cadherins is foundational. Cadherins nucleate complexes of dozens of proteins connecting junctions to the cytoskeleton and signaling downstream. Many junctional proteins are well-studied in epithelia but less is known about roles during mesenchymal migration. The nascent myotubes of the pupal Drosophila testis provide an excellent model for N-cadherin mediated mesenchymal migration. We combined a proximity proteomics dataset of adherens junction proteins in mammalian epithelial cells with genome-wide shRNA libraries knocking down Drosophila genes to begin to define the subset of junctional proteins important in mesenchymal migration. While N-cadherin is predominant, E-cadherin plays a supporting role. Surprisingly, several proteins with key roles in epithelial morphogenesis, including Afadin's homolog Canoe, ZO-1's homolog Polychaetoid, and Par3's homolog Bazooka play at most modest roles. Twenty-two genes with diverse cell biological roles had strong to moderate defects in testis morphogenesis. These will provide a community resource. We followed up two. The kinase Par-1 is important for migration and gap closure, with knockdown phenotypes paralleling those of myosin. The Rab GAP RN-tre does not have roles until after migration and works in parallel with N-cadherin during testis spiralization. [Media: see text] [Media: see text].

PMID:
42525541
Bibliographic data and abstract were imported from PubMed on 30 Jul 2026.

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