Decoding the Tubulin Code: Implications for Health and Disease

Microtubules are dynamic cytoskeletal polymers built from α/β-tubulin heterodimers that underlie fundamental cellular processes, including intracellular transport, cell division, ciliary and flagellar motility, and neuronal architecture. The functional diversity of microtubules across different cell types and physiological contexts is remarkable, especially given that tubulin is encoded by a limited set of genes. This diversity is largely achieved through the "tubulin code" - a combinatorial system comprising multiple tubulin isotypes and an extensive array of post-translational modifications (PTMs), such as acetylation, detyrosination, polyglutamylation, polyglycylation, and phosphorylation.These modifications, often concentrated on the microtubule surface or at the C-terminal tails of tubulin, regulate the recruitment and activity of microtubule-associated proteins (MAPs), motor proteins, and severing enzymes, thereby fine-tuning microtubule stability, dynamics, and interactions. Dysregulation of the tubulin code has been implicated in a growing number of human diseases, including neurodegenerative disorders, ciliopathies, cancer, and infertility, underscoring the urgent need to define how this code is dynamically written, read, and erased in physiological and pathological states.Despite significant progress, many aspects of the tubulin code remain poorly understood, including the precise enzymatic machinery involved, the structural consequences of specific modifications, and how combinations of PTMs and isotypes generate context-specific microtubule functions. This Research Topic aims to bring together current research and perspectives that advance our mechanistic and structural understanding of the tubulin code and its implications for health and disease.We welcome submissions addressing (but not limited to) the following themes:- Structural and biochemical characterization of tubulin isotypes and post-translational modifications.- Enzymes that write, read, or erase the tubulin code, including tubulin-modifying and de-modifying enzymes.- Regulation of microtubule-associated proteins (MAPs) and motor proteins by the tubulin code.- Role of the tubulin code in cilia and flagella structure, assembly, and motility.- Contribution of tubulin code dysregulation to neurodegenerative diseases and neurodevelopmental disorders.- Tubulin code alterations in cancer, drug resistance, and response to microtubule-targeting agents.- Tubulin code in reproductive biology and ciliopathies.- Advanced imaging, structural biology, and computational approaches for studying tubulin PTMs.- Evolutionary and comparative perspectives on tubulin isotype diversity and the tubulin code.- Emerging technologies and tools — including bioorthogonal chemical probes, expansion microscopy, and novel mass spectrometry workflows — for detecting, mapping, or manipulating tubulin modifications.We welcome original research, reviews, mini-reviews, perspectives, and FAIR2 Data articles. Topic editors: Krishna Kishore Mahalingan, Sudarshan Gadadhar, Kai He Source: https://www.frontiersin.org/research-topics/84669/decoding-the-tubulin-code-implications-for-health-and-disease