Polyglutamylation-Specific Antibody Introduction

Polyglutamylation is a post-translational modification (PTM) that forms glutamate side chains of varying lengths on the modified protein. It plays a crucial role in regulating of microtubule function and even different cellular activities. Polyglutamylation is essential for the regulation of neural function in the brain and serves as a therapeutic target for numerous neurological diseases. In-depth studies of polyglutamylation are particularly important due to its regulatory role in neurological diseases. Based on our hybridoma technology and phage display technology, Creative Biolabs offers a comprehensive service to support the development of polyglutamylation-specific antibodies.

Polyglutamylation Modification

Polyglutaminylation is a reversible post-translational modification. It is modified by the enzyme family of polyglutaminases, which conjugate a peptide chain with the carboxyl group at the γ position on the glutamate residue. These enzymes exhibit substrate specificity and reaction specificity. The glutamylation process begins by forming a covalent bond between the amino and γ-carboxyl groups of glutamate in the primary protein chain. The glutamate side chain then elongates through the successive additions of glutamate residues to the α-carboxyl group of the preceding glutamate. Polyglutamylation generates a substantial negative charge, regulating the interactions between microtubulin and other proteins to maintain microtubulin stability. Recent studies suggest that polyglutamylation has a broader modifying role and may act as a regulator in various cellular processes.

Ten years after the initial discovery of microtubulin polyglutamylation, two prominent non-microtubulin substrates, nucleosome assembly protein (NAP)2 and NAP10, were identified. Notably, NAPs were recently found to share another PTM with microtubulin—polyglycination. Although the glycosylases for microtubulin remain unidentified, TTLL10 has been shown to catalyze NAP glycosylation. However, TTLL10 belongs to the TTLL protein family, not the TTLL subgroup of polyglutaminases. Therefore, it is likely that microtubulin glycosylases also belongs to be members of the TTLL protein family. Moreover, proteomic approaches have identified over 100 proteins that specifically bind to the glutamylation-specific antibody GT335. Detailed analysis of these proteins led to the discovery of new substrates for polyglutamylation, including several chromatin-associated proteins. Specific TTLL polyglutaminases modify these new substrates, but the impact of polyglutamylation on their biological functions remains unknown. Nevertheless, the discovery of a wide range of substrates suggests that polyglutamylation is a general post-translational protein modification that should potentially regulates multiple cellular functions.

Furthermore, related studies demonstrate that in a mouse model, hyperpolyglutamylation of microtubules leads to an abundance of polyglutamylated microtubules, contributing to neurodegeneration. Microtubule loss is a common endpoint phenomenon in neurodegenerative diseases. Hyperglutamylation of free microtubule proteins has been shown to trigger endoplasmic reticulum stress, leading to the accumulation of unfolded proteins in a mouse model of neurodegenerative mutants.

Polyglutamylation-Specific Antibody

In general, specific antibodies required for our needs can be purchased commercially. However, customization is sometimes necessary to obtain antibodies that meet specific PTM (post-translational modification) requirements. Antibodies are commonly produced using hybridoma methods and phage display techniques. By combining relevant literature and specific experimental requirements, antibody development protocols can be designed and defined, resulting in scientific and efficient antibody production. Since there are no known modification sites for polyglutamylation, the development of antibodies usually begins with polyglutamylated microtubulin, which recognizes most forms of polyglutamylation regardless of the length of the glutamate side chain.

At Creative Biolabs, we have extensive knowledge and experience in PTM specific antibody discovery, including polyglutamylation. We would be delighted to discuss our expertise and experience in developing polyglutamylation-specific antibodies with you.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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