Reference Report

Reference
Citation	Zhang, S., Dailey, G.M., Kwan, E., Glasheen, B.M., Sroga, G.E., Page-McCaw, A. (2006). An MMP liberates the Ninjurin A ectodomain to signal a loss of cell adhesion. Genes Dev. 20(14): 1899--1910. (Export to RIS)
FlyBase ID	FBrf0192458
Publication Type	Research paper
PubMed ID	16815999
PubMed Abstract	Matrix metalloproteinases (MMPs) are important for developmental tissue remodeling and for the inflammatory response. Although the vertebrate MMP family is large and functionally redundant, the fruitfly Drosophila melanogaster has only two MMPs, both essential genes. Our previous work demonstrated that Mmp1 is required for growth of the tracheal system, and we suggested that the mutant phenotype resulted from aberrant persistence of cell adhesion to the extracellular matrix. Here we report the identification of NijA, a transmembrane protein whose vertebrate homologs regulate cell adhesion, as a two-hybrid binding partner for Mmp1. The binding of Mmp1 and NijA was confirmed by coimmunoprecipitation of endogenous proteins from flies, and the endogenous proteins were found to colocalize at the tracheal cell surface in larvae. When NijA is expressed in S2 cells, they lose adhesion to surfaces; this adhesion-loss phenotype is dependent on the expression and catalytic activity of Mmp1. Our data indicate that Mmp1 releases the N-terminal extracellular domain of NijA. This liberated ectodomain promotes the loss of cell adhesion in a cell-nonautonomous manner. We suggest that tracheal cell adhesion is regulated by a novel mechanism utilizing an MMP and a ninjurin family member.
DOI	10.1101/gad.1426906
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Genes Dev.
Title	Genes & Development
Publication Year	1987-
ISBN/ISSN	0890-9369
Data from Reference
Alleles (9)
	Mmp1^dsRNA.1.6kb Mmp1^{E225A.f1.MtnA} Mmp1^{E225A.f1.Scer\UAS} NijA^{1-161.EC1.Mtn.T:Ivir\HA1} NijA^{A.MtnA.T:Ivir\HA1} NijA^dsRNA.1.6kb Scer\GAL4^MtnA.PK Scer\GAL4^αTub84B.PL Timp^Scer\UAS.cPa
Constructs (3)
	P{tubP-GAL4} P{UAS-Mmp1.E225A.f1} P{UAS-Timp.P}
Genes (17)
	CG11110 CG17477 CG31661 CG31926 CG33128 CycB Dpse\GA11113 Dpse\GA12950 Dpse\GA19603 Jon66Cii Mmp1 NijA NijB NijC Scer\GAL4 Timp vir-1