Tousled-like kinase regulates cytokine-mediated communication between cooperating cell types during collective border cell migration.

TitleTousled-like kinase regulates cytokine-mediated communication between cooperating cell types during collective border cell migration.
Publication TypeJournal Article
Year of Publication2016
AuthorsXiang W, Zhang D, Montell DJ
JournalMol Biol Cell
Volume27
Issue1
Pagination12-9
Date Published2016 Jan 01
ISSN1939-4586
KeywordsAnimals, Cell Communication, Cell Differentiation, Cell Movement, Cytokines, DNA-Binding Proteins, Drosophila melanogaster, Drosophila Proteins, Epithelial Cells, Female, Male, Ovary, Polar Bodies, Protein-Serine-Threonine Kinases, Signal Transduction, STAT Transcription Factors, Trans-Activators, Transcription Factors
Abstract

<p>Collective cell migration is emerging as a major contributor to normal development and disease. Collective movement of border cells in the Drosophila ovary requires cooperation between two distinct cell types: four to six migratory cells surrounding two immotile cells called polar cells. Polar cells secrete a cytokine, Unpaired (Upd), which activates JAK/STAT signaling in neighboring cells, stimulating their motility. Without Upd, migration fails, causing sterility. Ectopic Upd expression is sufficient to stimulate motility in otherwise immobile cells. Thus regulation of Upd is key. Here we report a limited RNAi screen for nuclear proteins required for border cell migration, which revealed that the gene encoding Tousled-like kinase (Tlk) is required in polar cells for Upd expression without affecting polar cell fate. In the absence of Tlk, fewer border cells are recruited and motility is impaired, similar to inhibition of JAK/STAT signaling. We further show that Tlk in polar cells is required for JAK/STAT activation in border cells. Genetic interactions further confirmed Tlk as a new regulator of Upd/JAK/STAT signaling. These findings shed light on the molecular mechanisms regulating the cooperation of motile and nonmotile cells during collective invasion, a phenomenon that may also drive metastatic cancer. </p>

DOI10.1091/mbc.E15-05-0327
Alternate JournalMol. Biol. Cell
PubMed ID26510500
PubMed Central IDPMC4694751
Grant ListR01 GM046425 / GM / NIGMS NIH HHS / United States
GM46425 / GM / NIGMS NIH HHS / United States