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Citation
Vargas, E.J.M., Matamoros, A.J., Qiu, J., Jan, C.H., Wang, Q., Gorczyca, D., Han, T.W., Weissman, J.S., Jan, Y.N., Banerjee, S., Song, Y. (2020). The microtubule regulator ringer functions downstream from the RNA repair/splicing pathway to promote axon regeneration.  Genes Dev. 34(3-4): 194--208.
FlyBase ID
FBrf0244768
Publication Type
Research paper
Abstract

Promoting axon regeneration in the central and peripheral nervous system is of clinical importance in neural injury and neurodegenerative diseases. Both pro- and antiregeneration factors are being identified. We previously reported that the Rtca mediated RNA repair/splicing pathway restricts axon regeneration by inhibiting the nonconventional splicing of Xbp1 mRNA under cellular stress. However, the downstream effectors remain unknown. Here, through transcriptome profiling, we show that the tubulin polymerization-promoting protein (TPPP) ringmaker/ringer is dramatically increased in Rtca-deficient Drosophila sensory neurons, which is dependent on Xbp1. Ringer is expressed in sensory neurons before and after injury, and is cell-autonomously required for axon regeneration. While loss of ringer abolishes the regeneration enhancement in Rtca mutants, its overexpression is sufficient to promote regeneration both in the peripheral and central nervous system. Ringer maintains microtubule stability/dynamics with the microtubule-associated protein futsch/MAP1B, which is also required for axon regeneration. Furthermore, ringer lies downstream from and is negatively regulated by the microtubule-associated deacetylase HDAC6, which functions as a regeneration inhibitor. Taken together, our findings suggest that ringer acts as a hub for microtubule regulators that relays cellular status information, such as cellular stress, to the integrity of microtubules in order to instruct neuroregeneration.

PubMed ID
PubMed Central ID
PMC7000917 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Genes Dev.
    Title
    Genes & Development
    Publication Year
    1987-
    ISBN/ISSN
    0890-9369
    Data From Reference
    Aberrations (1)
    Alleles (14)
    Genes (11)
    Physical Interactions (6)
    Natural transposons (1)
    Insertions (1)
    Experimental Tools (1)
    Transgenic Constructs (5)