The impact of the tubulin-code on lifelong neuronal function and homeostasis

Touch receptor neurons as a model system to study the impact of the tubulin code

Microtubules (MTs) are key cytoskeletal polymers involved in maintaining cell polarity, axon outgrowth and serve as a track for transporting different cargoes in all eukaryotic cells. Cells modulate their MTs structure and functions by expressing various alpha and beta-tubulin isoforms and different post-translational modifications (PTMs) enzymes. The tubulin code hypothesis states that the diversity of tubulin isoforms and PTMs assigns unique identities to MTs so that they can perform a large variety of functions across various cell types [1]. A growing body of evidence suggests that small perturbations in tubulin code leads to a wide range of age-associated neurodegenerative diseases. However, little is known about the role of the tubulin code in maintaining MT structure and functions in neuronal cells throughout the life of an organism. 

In this project, we study the effect of the tubulin code on neuronal trafficking and aging, using the touch receptor neurons in C. elegans. We use PTMs null mutants and age or time-dependent depletion of each desired PTM protein with the help of CRISPR/Cas9 and Auxin inducible degron (AID) system. We also follow neuronal trafficking in real-time using novel microfluidics approaches tailored to adult C. elegans animals. 

References

[1] Janke & Mageira (2020), The tubulin code and its role in controlling microtubule properties and functions, Nature Reveiws Molecula Cell Biology

[2] Mageira et al. (2018), Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport, The EMBO Journal

[3] Shashi et al. Loss of tubulin deglutamylase CCP 1 causes infantile‐onset neurodegeneration, The EMBO Journal