The protein tubulin plays a crucial role in cell structure and function, forming the main component of microtubules. Researchers from EPFL and the University of Geneva have made significant progress in understanding the mechanisms behind tubulin post-translational modifications (PTMs). By engineering tubulin with specific modifications, they have gained valuable insights into the interplay between different PTMs and their impact on tubulin’s role within cells. This breakthrough has the potential to advance our understanding of tubulin’s molecular function and its relevance to disease progression.
Led by Professors Beat Fierz and Assistant Professor Charlotte Aumeier, the study utilized a chemical method to engineer fully functional tubulin with precise combinations of PTMs. By using chemo-enzymatic protein splicing, synthetic alpha-tubulin tails were attached to human tubulin molecules, modified with varying degrees of polyglutamate. This technique allowed the researchers to assemble microtubules with homogenous modifications, providing new insights into the role of specific PTMs in tubulin function.
The study revealed that polyglutamylation of alpha-tubulin enhances the activity of the vasohibin/SVBP protein complex, the key enzyme responsible for detyrosination. By altering the levels of polyglutamate in living cells, the researchers observed the effects on tyrosine removal, confirming the importance of this PTM in regulating tubulin function. These findings shed light on the intricate interplay between polyglutamylation and detyrosination in controlling tubulin function, providing novel insights into the regulatory systems governing this protein.
Tubulin PTMs and Disease
Dysregulation of tubulin PTMs has been associated with various diseases. Understanding the importance of these modifications for disease progression is crucial for developing potential therapies. The ability to engineer tubulins with specific PTMs opens up new avenues for studying tubulin dysregulation and developing targeted therapeutic strategies. By gaining a deeper understanding of the molecular function of tubulin and the impact of dysregulated PTMs, researchers can work towards novel treatments for diseases related to tubulin dysfunction.
Building on this work, the labs of Fierz and Aumeier, in collaboration with Jens Stein at the University of Fribourg and Michael Sixt at ISTA Vienna, plan to investigate how tubulin PTMs influence the cytoskeleton in migrating immune cells. This research holds promise for uncovering new insights into cell migration and immune system functionality. By studying the effects of PTMs on the dynamics of the cytoskeleton in immune cells, researchers can gain a comprehensive understanding of the role of tubulin in cell migration and potentially develop therapies targeting immune response dysfunctions.
The study conducted by researchers from EPFL and the University of Geneva has provided significant advancements in our understanding of tubulin PTMs. By engineering tubulin with specific modifications, researchers have gained valuable insights into the interplay between different PTMs and their impact on tubulin’s role within cells. This knowledge opens up new avenues for studying diseases related to tubulin dysregulation and developing potential therapeutic strategies. With the ability to fine-tune tubulin PTMs, researchers can further explore the molecular function of tubulin and its relevance to various diseases.
Leave a Reply