RRC ID 50325
著者 Donohoe CD, Csordás G, Correia A, Jindra M, Klein C, Habermann B, Uhlirova M.
タイトル Atf3 links loss of epithelial polarity to defects in cell differentiation and cytoarchitecture.
ジャーナル PLoS Genet
Abstract Interplay between apicobasal cell polarity modules and the cytoskeleton is critical for differentiation and integrity of epithelia. However, this coordination is poorly understood at the level of gene regulation by transcription factors. Here, we establish the Drosophila activating transcription factor 3 (atf3) as a cell polarity response gene acting downstream of the membrane-associated Scribble polarity complex. Loss of the tumor suppressors Scribble or Dlg1 induces atf3 expression via aPKC but independent of Jun-N-terminal kinase (JNK) signaling. Strikingly, removal of Atf3 from Dlg1 deficient cells restores polarized cytoarchitecture, levels and distribution of endosomal trafficking machinery, and differentiation. Conversely, excess Atf3 alters microtubule network, vesicular trafficking and the partition of polarity proteins along the apicobasal axis. Genomic and genetic approaches implicate Atf3 as a regulator of cytoskeleton organization and function, and identify Lamin C as one of its bona fide target genes. By affecting structural features and cell morphology, Atf3 functions in a manner distinct from other transcription factors operating downstream of disrupted cell polarity.
巻・号 14(3)
ページ e1007241
公開日 2018-3-1
DOI 10.1371/journal.pgen.1007241
PII PGENETICS-D-17-02089
PMID 29494583
PMC PMC5849342
MeSH Activating Transcription Factor 3 / genetics Activating Transcription Factor 3 / metabolism* Animals Animals, Genetically Modified Cell Differentiation Cell Polarity / physiology* Chromatin Immunoprecipitation Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / cytology Drosophila melanogaster / genetics Endosomes / metabolism Eye / growth & development Imaginal Discs / cytology Imaginal Discs / physiology Lamin Type A / genetics Lamin Type A / metabolism Larva MAP Kinase Signaling System Membrane Proteins Nucleotide Motifs / physiology Protein Kinase C / metabolism Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism
IF 5.175
引用数 5
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