Rap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions in Collective Cell Migration.

TitleRap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions in Collective Cell Migration.
Publication TypeJournal Article
Year of Publication2018
AuthorsChang Y-C, Wu J-W, Hsieh Y-C, Huang T-H, Liao Z-M, Huang Y-S, Mondo JA, Montell D, Jang AC-C
JournalCell Rep
Volume22
Issue8
Pagination2160-2175
Date Published2018 02 20
ISSN2211-1247
KeywordsActomyosin, Animals, Cell Movement, Cell Polarity, Cell Surface Extensions, Drosophila melanogaster, Drosophila Proteins, Epistasis, Genetic, Intracellular Signaling Peptides and Proteins, Models, Biological, Protein-Serine-Threonine Kinases, Signal Transduction, Telomere-Binding Proteins
Abstract

<p>In collective cell migration, directional protrusions orient cells in response to external cues, which requires coordinated polarity among the migrating cohort. However, the molecular mechanism has not been well defined. Drosophila border cells (BCs) migrate collectively and invade via the confined space between nurse cells, offering an in vivo model to examine how group polarity is organized. Here, we show that the front/back polarity of BCs requires Rap1, hyperactivation of which disrupts cluster polarity and induces misoriented protrusions and loss of asymmetry in the actin network. Conversely, hypoactive Rap1 causes fewer protrusions and cluster spinning during migration. A forward genetic screen revealed that downregulation of the Hippo (Hpo) pathway core components hpo or mats enhances the Rap1-induced migration defect and misdirected protrusions. Mechanistically, association of Rap1 with the kinase domain of Hpo suppresses its activity, which releases Hpo signaling-mediated suppression of F-actin elongation, promoting cellular protrusions in collective cell migration.</p>

DOI10.1016/j.celrep.2018.01.080
Alternate JournalCell Rep
PubMed ID29466741