Chapter 16 - Polyglutamylation and the fleer Gene

Abstract

The zebrafish fleer gene is a homolog of Caenorhabditis elegans dyf-1 and encodes a tetratricopeptide repeat (TPR) repeat protein that is a component of the cilia proteome. fleer is essential for cilia function and its deficiency reduces cilia tubulin glutamylation in zebrafish, disrupts OSM-3 kinesin-dependent assembly of the singlet microtubule of C. elegans amphid cilia and induces B-tubule structural defects. fleer is highly expressed in ciliated cells, localizes to cilia, and regulates tubulin glutamylation selectively within the cilia axoneme. Polyglutamylation is a posttranslational tubulin modification that modulates charge-based protein interactions of microtubules by enhancing their electronegative character. Polyglutamylated tubulins are abundant in stable microtubule-rich organelles: cilia, centrioles, and neuronal axons. This chapter describes tubulin polyglutamylation with respect to cilia structure and function and provides a synopsis of zebrafish cilia defects in the fleer mutant as a reference for using zebrafish to study the in vivo significance and enzymatic mechanisms of tubulin glutamylation.