RRC ID 34880
著者 Wang Y, Antunes M, Anderson AE, Kadrmas JL, Jacinto A, Galko MJ.
タイトル Integrin Adhesions Suppress Syncytium Formation in the Drosophila Larval Epidermis.
ジャーナル Curr Biol
Abstract Integrins are critical for barrier epithelial architecture. Integrin loss in vertebrate skin leads to blistering and wound healing defects. However, how integrins and associated proteins maintain the regular morphology of epithelia is not well understood. We found that targeted knockdown of the integrin focal adhesion (FA) complex components β-integrin, PINCH, and integrin-linked kinase (ILK) caused formation of multinucleate epidermal cells within the Drosophila larval epidermis. This phenotype was specific to the integrin FA complex and not due to secondary effects on polarity or junctional structures. The multinucleate cells resembled the syncytia caused by physical wounding. Live imaging of wound-induced syncytium formation in the pupal epidermis suggested direct membrane breakdown leading to cell-cell fusion and consequent mixing of cytoplasmic contents. Activation of Jun N-terminal kinase (JNK) signaling, which occurs upon wounding, also correlated with syncytium formation induced by PINCH knockdown. Further, ectopic JNK activation directly caused epidermal syncytium formation. No mode of syncytium formation, including that induced by wounding, genetic loss of FA proteins, or local JNK hyperactivation, involved misregulation of mitosis or apoptosis. Finally, the mechanism of epidermal syncytium formation following JNK hyperactivation and wounding appeared to be direct disassembly of FA complexes. In conclusion, the loss-of-function phenotype of integrin FA components in the larval epidermis resembles a wound. Integrin FA loss in mouse and human skin also causes a wound-like appearance. Our results reveal a novel and unexpected role for proper integrin-based adhesion in suppressing larval epidermal cell-cell fusion--a role that may be conserved in other epithelia.
巻・号 25(17)
ページ 2215-27
公開日 2015-8-31
DOI 10.1016/j.cub.2015.07.031
PII S0960-9822(15)00834-9
PMID 26255846
PMC PMC4558245
MeSH Animals Drosophila / genetics* Drosophila / growth & development Drosophila / metabolism Drosophila Proteins / genetics* Drosophila Proteins / metabolism Epidermis / growth & development Epidermis / metabolism Gene Knockdown Techniques Giant Cells / metabolism Integrin beta Chains / genetics* Integrin beta Chains / metabolism Larva / growth & development Larva / metabolism Protein Serine-Threonine Kinases / genetics* Protein Serine-Threonine Kinases / metabolism Pupa / growth & development Pupa / metabolism Transcription Factors / genetics* Transcription Factors / metabolism
IF 9.601
引用数 13
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ショウジョウバエ 7954R-1 1560R-2 5680R-1 5680R-3 3722R-1 1725R-1 1725R-2 5055R-1 5055R-2 7954R-1