The PS2 integrin ligand tiggrin is required for proper muscle function in Drosophila

Abstract

Tiggrin is a novel extracellular matrix ligand for the Drosophila PS2 integrins. We have used flanking P elements to generate a precise deletion of tiggrin. Most flies lacking tiggrin die as larvae or pupae. A few adults do emerge and these appear to be relatively normal, displaying only misshapen abdomens and a low frequency of wing defects. Examination of larvae shows that muscle connections, function and morphology are defective in tiggrin mutants. Muscle contraction waves that extend the length of the larvae are much slower in tiggrin mutants. Direct examination of bodywall muscles shows defects in muscle attachment sites, where tiggrin is specifically localized, and muscles appear thinner. Transgenes expressing tiggrin are capable of rescuing tiggrin mutant phenotypes. Transgenes expressing a mutant tiggrin, whose Arg-Gly-Asp (RGD) integrin recognition sequence has been mutated to Leu-Gly-Ala (LGA) show much reduced, but significant, rescuing ability. Cell spreading assays detect no interactions of this mutant tiggrin with PS2 integrins. Therefore, while the RGD sequence is critical for PS2 interactions and full activity in the whole fly, the mutant tiggrin retains some function(s) that are probably mediated by interactions with other ECM molecules or cell surface receptors

Integrins are required for synchronous ommatidial rotation in the Drosophila eye linking planar cell polarity signalling to the extracellular matrix

“…Perlecan, a heparan sulfate proteoglycan, binds to other ECM molecules including laminins. Laminin-α1/2 and Tiggrin, in turn, directly bind to βPS integrins [64,65]. Interestingly, we also observed a dominant enhancement of sev > mys by Syndecan mutants (sdc 10608 ; table 1).…”

Chitin deacetylases are necessary for insect femur muscle attachment and mobility

“…Relatively few studies have focused on the relationship between insect exoskeletal cuticle development in concert with limb muscle and internal tendon cuticle development, microstructure, and locomotion ( 9 , 18 , 33 – 36 ). Besides the transmembrane integrins, several integrin-binding proteins—such as tiggrin, thrombospondin, and laminins—are involved in cell–cell and cell–matrix adhesion ( 38 – 41 ). D. melanogaster pupal lethal fon mutant larvae that are deficient in this secreted ECM protein also have detached muscles and decreased larval motility ( 41 ).…”

Developmental origin of tendon diversity in Drosophila melanogaster

“…However, others remain to be identified. For instance, a subset of proteins involved in hemolymph clotting, Fondue (Fon), the integrin-associated protein Tiggrin (Tig) and the Larval Serum Protein 1 Gamma (Lsp1), have been shown to accumulate at the junction between larval muscles and their respective attachment sites and to participate to the MAS architecture ( Fogerty et al, 1994 ; Bunch et al, 1998 ; Green et al, 2016 ).…”