Formin 3 stabilizes the cytoskeleton of Drosophila tendon cells, thus enabling them to resist muscle tensile forces.

Abstract

The cytoskeleton of Drosophila tendon cells features specialized F-actin/microtubule arrays that endow these cells with resistance to the tensile forces exerted by the attached muscles. In a forward genetic screen for mutants with neuromuscular junction and muscle morphology phenotypes in larvae, we identified formin 3 (form3) as a crucial component for stabilizing these cytoskeletal arrays under muscle tension. form3 mutants exhibit severely stretched tendon cells in contact with directly attached larval body wall muscles, leading to muscle retraction and rounding. Both the actomyosin and microtubule arrays are expanded likewise in these mutants and can separate laterally in extreme cases. The analysis of a natively HA-tagged, functional version of Form3 reveals that Form3 is distributed along the length of these cytoskeletal arrays. Based on our findings and existing data on vertebrate and C. elegans orthologs of form3, we propose that Form3's primary function in this context is to co-bundle actin filaments and microtubules, thus maximizing the rigidity of these cytoskeletal structures against muscle tensile forces.