Gammaglutamylation

Gammaglutamylation is a post-translational modification where a glutamate residue is attached to another protein or to a second glutamate residue on the same protein. This process is catalyzed by specific enzymes known as gamma-glutamyl ligases. The most well-studied example of gammaglutamylation is the addition of a second glutamate to the C-terminus of certain proteins, particularly those involved in calcium signaling and protein trafficking. This modification often occurs on glutamate-rich proteins such as tubulin, where it plays a crucial role in regulating microtubule dynamics and stability. The addition of these gamma-glutamyl chains can create isoforms of proteins with altered functional properties. For instance, highly glutamylated tubulin is a hallmark of stable microtubules found in neuronal axons and cilia. Gammaglutamylation is a reversible process, and the removal of gamma-glutamyl chains is carried out by de-glutamylase enzymes, allowing for dynamic regulation of cellular processes. Aberrant gammaglutamylation has been implicated in various neurological disorders, highlighting its importance in maintaining cellular homeostasis and function.