The adaptor protein Cindr regulates JNK activity to maintain epithelial sheet integrity

Developmental biology

Hannah W.R.Yasin¹ 

关键词: CP;    actin-capping protein;    AJ;    adherens junction;    APF;    after puparium formation;    A/P;    anterior/posterior;    Bsk;    basket;    β-Gal;    β-Galactosidase;    JNK;    c-Jun N-terminal kinase;    Chic;    chickadee;    Dcr-2;    dicer-2;    D/V;    dorsal/ventral;    dJNK;    Drosophila JNK;    Jra or dJun;    Drosophila Jun;    Ecad;    ecadherin;    GMA;    GFP:moesin-Actin-binding-domain;    GFP;    green fluorescent protein;    GAPs;    GTPase activating proteins;    Hid;    hid involution defective;    MMP;    matrixmetalloprotease;    Ptc;    patched;    Puc;    puckered;    RTK;    receptor tyrosine kinase;    Slpr;    slipper;    TdT;    terminal deoxynucleotidyl transferase;    TUNEL;    mediated dUTP nick end labeling;    ZA;    zonula adherens;    Cindr;    Cd2ap;    Cin85;    JNK;    Epithelial integrity;   

DOI  :  10.1016/j.ydbio.2016.01.003

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Epithelia are essential barrier tissues that must be appropriately maintained for their correct function. To achieve this a plethora of protein interactions regulate epithelial cell number, structure and adhesion, and differentiation. Here we show that Cindr (the Drosophila Cin85 and Cd2ap ortholog) is required to maintain epithelial integrity. Reducing Cindr triggered cell delamination and movement. Most delaminating cells died. These behaviors were consistent with JNK activation previously associated with loss of epithelial integrity in response to ectopic oncogene activity. We confirmed a novel interaction between Cindr and Drosophila JNK (dJNK), which when perturbed caused inappropriate JNK signaling. Genetically reducing JNK signaling activity suppressed the effects of reducing Cindr. Furthermore, ectopic JNK signaling phenocopied loss of Cindr and was partially rescued by concomitant cindr over-expression. Thus, correct Cindr-dJNK stoichiometry is essential to maintain epithelial integrity and disturbing this balance may contribute to the pathogenesis of disease states, including cancer.

【 授权许可】

CC BY