The deubiquitinating enzyme UBPy/USP8 interacts with TrkA and inhibits neuronal differentiation in PC12 cells
| Autor: | Giovanna Berruti, Michela Ceriani, Enzo Martegani, Loredana Amigoni, Alessia D’Aloia |
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| Přispěvatelé: | Ceriani, M, Amigoni, L, D'Aloia, A, Berruti, G, Martegani, E |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
animal structures
Neurite Cellular differentiation Signaling endosome Endosomes Tropomyosin receptor kinase A PC12 Cells Receptor tyrosine kinase Nerve Growth Factor medicine Low-affinity nerve growth factor receptor Animals Humans Receptor trkA USP8/UBPy PC12 cell Neurons biology TrkA Ubiquitination Cell Differentiation Cell Biology BIO/11 - BIOLOGIA MOLECOLARE Molecular biology Sensory neuron Rats Protein Transport Nerve growth factor medicine.anatomical_structure HEK293 Cells nervous system Trk receptor Differentiation Proteolysis biology.protein Deubiquitination Ubiquitin-Specific Proteases |
| Popis: | The tropomyosin-related kinase (Trk) family of receptor tyrosine kinases controls synaptic function, plasticity and sustains differentiation, morphology, and neuronal cell survival. Understanding Trk receptors down-regulation and recycling is a crucial step to point out sympathetic and sensory neuron function and survival. PC12 cells derived from pheochromocytoma of the rat adrenal medulla have been widely used as a model system for studies of neuronal differentiation as they respond to nerve growth factor (NGF) with a dramatic change in phenotype and acquire a number of properties characteristic of sympathetic neurons. In this study we demonstrated that in PC12 cells the TrkA receptor interacts with the deubiquitinating enzyme USP8/UBPy in a NGF-dependent manner and that it is deubiquitinated in vivo and in vitro by USP8. USP8 overexpression blocked NGF-induced neurites outgrowth while the overexpression of the catalytically inactive mutant USP8/UBPy(C748A) caused a marked increase of cell differentiation. Localization and biochemical experiments have point out that USP8 and TrkA partially co-localize in endosomes after NGF stimulation. Finally we have studied the role played by USP8 on TrkA turnover; using specific siRNA for USP8 we found that USP8 knockdown increases TrkA half-life, suggesting that the deubiquitinating activity of USP8 promotes TrkA degradation. |
| Databáze: | OpenAIRE |
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