Artículo
HERC1 Ubiquitin Ligase Is Required for Normal Axonal Myelination in the Peripheral Nervous System
Autor/es | Bachiller, Sara
Roca Ceballos, María Angustias García Domínguez, Irene Pérez Villegas, Eva María Martos Carmona, David Pérez Castro, Miguel Ángel Real Navarrete, Luis Miguel Rosa, José Luis Tabares, Lucía Venero Recio, José Luis Armengol, José Ángel Carrión, Ángel Manuel Ruiz Laza, Rocío |
Departamento | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
Fecha de publicación | 2018-03-30 |
Fecha de depósito | 2024-02-12 |
Publicado en |
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Resumen | A missense mutation in HERC1 provokes loss of cerebellar Purkinje cells, tremor, and unstable gait in tambaleante (tbl) mice. Recently, we have shown that before cerebellar degeneration takes place, the tbl mouse suffers ... A missense mutation in HERC1 provokes loss of cerebellar Purkinje cells, tremor, and unstable gait in tambaleante (tbl) mice. Recently, we have shown that before cerebellar degeneration takes place, the tbl mouse suffers from a reduction in the number of vesicles available for release at the neuromuscular junction (NMJ). The aim of the present work was to study to which extent the alteration in HERC1 may affect other cells in the nervous system and how this may influence the motor dysfunction observed in these mice. The functional analysis showed a consistent delay in the propagation of the action potential in mutant mice in comparison with control littermates. Morphological analyses of glial cells in motor axons revealed signs of compact myelin damage as tomacula and local hypermyelination foci. Moreover, we observed an alteration in non-myelinated terminal Schwann cells at the level of the NMJ. Additionally, we found a significant increment of phosphorylated Akt-2 in the sciatic nerve. Based on these findings, we propose a molecular model that could explain how mutated HERC1 in tbl mice affects the myelination process in the peripheral nervous system. Finally, since the myelin abnormalities found in tbl mice are histological hallmarks of neuropathic periphery diseases, tbl mutant mice could be considered as a new mouse model for this type of diseases. |
Agencias financiadoras | Dirección General de Investigación Científica y Técnica (DGICYT). España Fundación Ramón Areces Ministerio de Economía y Competitividad (MINECO). España Junta de Andalucía |
Identificador del proyecto | BFU2011-27207
BFU2015-64536-R SAF2015-64171-R C-0009-2015 |
Cita | Bachiller, S., Roca Ceballos, M.A., García Domínguez, I., Pérez Villegas, E.M., Martos Carmona, D., Pérez Castro, M.Á.,...,Ruiz Laza, R. (2018). HERC1 Ubiquitin Ligase Is Required for Normal Axonal Myelination in the Peripheral Nervous System. Molecular Neurobiology, 55 (112), 8856-8868. https://doi.org/10.1007/s12035-018-1021-0. |
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