Tubulin Polyglutamylase Complex Subunit 2 (TPGS2) is a crucial component of the neuronal polyglutamylase complex. This complex plays a significant role in the post-translational modification of tubulin, specifically through the addition of glutamate residues to the C-terminal tails of tubulin. This modification is essential for the proper functioning of microtubules, which are critical components of the cytoskeleton in eukaryotic cells.
The TPGS2 protein is involved in the polyglutamylation of tubulin, a process that affects the stability and function of microtubules. Polyglutamylation is a type of post-translational modification where glutamate residues are added to the gamma-carboxyl group of glutamate residues in proteins. This modification is particularly important in the regulation of microtubule-associated proteins and motor proteins, which are essential for intracellular transport and cell division.
The tubulin polyglutamylase complex, which includes TPGS2, is vital for the biogenesis and motility of cilia and flagella. These structures are essential for cell movement and sensory functions. In neurons, polyglutamylation of tubulin by TPGS2 is crucial for the proper functioning of axonal transport, which is necessary for the maintenance and function of neuronal cells .
The gene encoding TPGS2 is located on chromosome 15 in humans. It has been observed that there are multiple alternatively spliced transcript variants encoding different isoforms of this protein. This diversity in isoforms allows for the fine-tuning of tubulin polyglutamylation in various tissues and developmental stages .
Mutations or dysregulation of TPGS2 and the tubulin polyglutamylase complex can lead to various diseases. For instance, defects in this complex have been associated with ciliopathies, which are disorders caused by dysfunctional cilia. These conditions can lead to a wide range of symptoms, including respiratory problems, kidney disease, and retinal degeneration .
Recombinant TPGS2 is used in research to study the mechanisms of tubulin polyglutamylation and its effects on cellular functions. Understanding the role of TPGS2 in microtubule dynamics can provide insights into the development of therapeutic strategies for diseases related to ciliary dysfunction and neuronal transport .