|  Help  |  About  |  Contact Us

Publication : Loss of tubulin deglutamylase CCP1 causes infantile-onset neurodegeneration.

First Author  Shashi V Year  2018
Journal  EMBO J Volume  37
Issue  23 PubMed ID  30420557
Mgi Jnum  J:270911 Mgi Id  MGI:6276488
Doi  10.15252/embj.2018100540 Citation  Shashi V, et al. (2018) Loss of tubulin deglutamylase CCP1 causes infantile-onset neurodegeneration. EMBO J 37(23)
abstractText  A set of glutamylases and deglutamylases controls levels of tubulin polyglutamylation, a prominent post-translational modification of neuronal microtubules. Defective tubulin polyglutamylation was first linked to neurodegeneration in the Purkinje cell degeneration (pcd) mouse, which lacks deglutamylase CCP1, displays massive cerebellar atrophy, and accumulates abnormally glutamylated tubulin in degenerating neurons. We found biallelic rare and damaging variants in the gene encoding CCP1 in 13 individuals with infantile-onset neurodegeneration and confirmed the absence of functional CCP1 along with dysregulated tubulin polyglutamylation. The human disease mainly affected the cerebellum, spinal motor neurons, and peripheral nerves. We also demonstrate previously unrecognized peripheral nerve and spinal motor neuron degeneration in pcd mice, which thus recapitulated key features of the human disease. Our findings link human neurodegeneration to tubulin polyglutamylation, entailing this post-translational modification as a potential target for drug development for neurodegenerative disorders.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

8 Bio Entities

Trail: Publication

0 Expression