Integrin signaling downregulates filopodia in muscle-tendon attachment


Type
Article
Change log
Authors
Richier, Benjamin 
Inoue, Yoshiko 
Friedlander, Jonathan 
Abstract

Cells need to sense their environment to ensure accurate targeting to specific destinations. This occurs in developing muscles, which need to attach to tendon cells before muscle contractions can begin. Elongating myotube tips form filopodia, which are presumed to have sensory roles, and are later suppressed upon building the attachment site. Here, we use live imaging and quantitative image analysis of lateral transverse (LT) myotubes in Drosophila to show that filopodia suppression occurs as a result of integrin signaling. Loss of the integrin subunits PS2 and PS increased filopodia number and length at stages when they are normally suppressed. Conversely, inducing integrin signaling, achieved by expression of constitutively dimerised PS cytoplasmic domain (di), prematurely suppressed filopodia. We discovered that the integrin signal is transmitted through the protein Git (G-protein receptor coupled interacting protein) and its downstream kinase Pak (p21-activated kinase). Absence of these proteins causes profuse filopodia and prevents filopodial inhibition by di. Thus, integrin signaling terminates the exploratory behaviour of myotubes seeking tendons, enabling the actin machinery to focus on forming a strong attachment and assembling the contractile apparatus.

Description
Keywords
Actin dynamics, Drosophila, Filopodia, Integrin signaling, Muscle, Animals, Animals, Genetically Modified, Cell Communication, Down-Regulation, Drosophila, Embryo, Nonmammalian, Integrins, Muscle Development, Muscle, Skeletal, Pseudopodia, Signal Transduction, Tendons
Journal Title
Journal of Cell Science
Conference Name
Journal ISSN
1477-9137
1477-9137
Volume Title
131
Publisher
The Company of Biologists Ltd.
Sponsorship
European Research Council (281971)
Wellcome Trust (105602/Z/14/Z)
Wellcome Trust (095829/Z/11/Z)
Wellcome Trust (086451/Z/08/Z)
Wellcome Trust (069943/Z/02/Z)
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)