The Role of Talin Isoforms in Caenorhabditis elegans Gonad Morphogenesis and Muscle Function

Abstract

Talin (tln-1) is an important component of cell adhesion sites; it binds and activates integrins, linking extracellular matrix (ECM) components to cytoskeletal elements like actin and vinculin. In the nematode C. elegans, tln-1 is necessary for muscle contractility and gonadal leader cell migration. Loss of talin leads to whole-body paralysis as well as defects in distal tip cell (DTC) migration, the process that drives gonad morphogenesis. In C. elegans, tln-1 is predicted to exist as two additional, shorter splice isoforms (tln-1b, tln-1c). Tln-1b is purported to mostly encode the integrin-binding talin head domain, while tln-1c is predicted to encode most of the vinculin- and actin- binding talin rod domain. In this study, we sought to confirm the existence of these splice isoforms and determine their functions in C. elegans gonadal and muscle tissue. We identified tln-1b and tln-1c transcripts in C. elegans cDNA through RT-PCR and used isoform-specific RNAi feeding experiments to explore the roles of tln-1b and tln-1c in muscle function and distal tip cell migration. We demonstrated that loss of tln-1b causes total body paralysis and, when against a sensitized background of reduced integrin expression, defects in gonad morphology. Our results suggest that tln-1b is important for muscle function and DTC migration. Its role in both is likely linked to the activity of integrin heterodimers. The specific functions of tln-1c, however, remain to be elucidated, as we were unable to identify any phenotypes associated with loss of tln-1c alone. These findings elevate our understanding of talin protein isoforms; they carry important implications for developmental processes that stem from the integrity of cell migration and adhesion as well as for diseases that result from the loss of these functions.