Retrograde degenerative signaling mediated by the p75 neurotrophin receptor requires p150(Glued) deacetylation by axonal HDAC1
| Autor: | Eran Perlson, Dylan T. Burnette, Deyu Li, Patrizia Casaccia, Natalie Wallace, F. Edward Hickman, Emily M. Stanley, Shani Gluska, Sabine Fuhrmann, Bruce D. Carter, Amrita Pathak, Bryson M. Brewer, Francisca C. Bronfman, Katerina Akassoglou |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Protein subunit Dynein Histone Deacetylase 1 Axonal Transport Receptor Nerve Growth Factor General Biochemistry Genetics and Molecular Biology Article Rats Sprague-Dawley 03 medical and health sciences medicine Low-affinity nerve growth factor receptor Animals Axon Molecular Biology Neurons biology Cell Biology Dynactin Complex HDAC1 Axons Cell biology 030104 developmental biology medicine.anatomical_structure nervous system Axoplasmic transport Dynactin biology.protein sense organs Microtubule-Associated Proteins Developmental Biology Neurotrophin |
| Popis: | During development, neurons undergo apoptosis if they do not receive adequate trophic support from tissues they innervate or when detrimental factors activate the p75 neurotrophin receptor (p75NTR) at their axon ends. Trophic factor deprivation (TFD) or activation of p75NTR in distal axons results in a retrograde degenerative signal. However, the nature of this signal and the regulation of its transport are poorly understood. Here, we identify p75NTR intracellular domain (ICD) and histone deacetylase 1 (HDAC1) as part of a retrograde proapoptotic signal generated in response to TFD or ligand binding to p75NTR in sympathetic neurons. We report an unconventional function of HDAC1 in retrograde transport of a degenerative signal and its constitutive presence in sympathetic axons. HDAC1 deacetylates dynactin subunit p150(Glued), which enhances its interaction with dynein. These findings define p75NTR ICD as a retrograde degenerative signal and reveal p150(Glued) deacetylation as a unique mechanism regulating axonal transport. |
| Databáze: | OpenAIRE |
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