CalpB modulates border cell migration in <it>Drosophila</it> egg chambers

• Main Authors: Kókai Endre, Páldy Ferencz, Somogyi Kálmán, Chougule Anil, Pál Margit, Kerekes Éva, Deák Péter, Friedrich Péter, Dombrádi Viktor, Ádám Géza
• Format: Article
• Language: English
• Published: BMC 2012-07-01
• Series: BMC Developmental Biology
• Subjects: Cell motility; Proteolysis; Focal adhesion; Calpain; Talin; Integrins
• Online Access: http://www.biomedcentral.com/1471-213X/12/20

<p>Abstract</p> <p>Background</p> <p>Calpains are calcium regulated intracellular cysteine proteases implicated in a variety of physiological functions and pathological conditions. The <it>Drosophila melanogaster</it> genome contains only two genes, <it>CalpA</it> and <it>CalpB</it> coding for canonical, active calpain enzymes. The movement of the border cells in <it>Drosophila</it> egg chambers is a well characterized model of the eukaryotic cell migration. Using this genetically pliable model we can investigate the physiological role of calpains in cell motility.</p> <p>Results</p> <p>We demonstrate at the whole organism level that <it>CalpB</it> is implicated in cell migration, while the structurally related <it>CalpA</it> paralog can not fulfill the same function. The downregulation of the <it>CalpB</it> gene by mutations or RNA interference results in a delayed migration of the border cells in <it>Drosophila</it> egg chambers. This phenotype is significantly enhanced when the focal adhesion complex genes encoding for α-PS2 integrin ( <it>if</it>), β-PS integrin ( <it>mys</it>) and talin ( <it>rhea</it>) are silenced. The reduction of <it>CalpB</it> activity diminishes the release of integrins from the rear end of the border cells. The delayed migration and the reduced integrin release phenotypes can be suppressed by expressing wild-type talin-head in the border cells but not talin-head^R367A, a mutant form which is not able to bind β-PS integrin. CalpB can cleave talin <it>in vitro,</it> and the two proteins coimmunoprecipitate from <it>Drosophila</it> extracts.</p> <p>Conclusions</p> <p>The physiological function of <it>CalpB</it> in border cell motility has been demonstrated in <it>vivo</it>. The genetic interaction between the <it>CalpB</it> and the <it>if</it>, <it>mys,</it> as well as <it>rhea</it> genes, the involvement of active talin head-domains in the process, and the fact that CalpB and talin interact with each other collectively suggest that the limited proteolytic cleavage of talin is one of the possible mechanisms through which CalpB regulates cell migration.</p>