Abstract
The prion protein (PrP) is currently one of the most studied molecules in the neurosciences. It is the main cause of a group of neurological diseases collectively called transmissible spongiform encephalopathies that severely affect both humans and a variety of mammals. Much effort has been directed to understanding the molecular basis of PrP activity, both in physiological and pathological terms. In this context, identification of neuronally-relevant interactors of PrP may play a crucial role. We recently discovered a specific, high-affinity (nanomolar KD) interaction with tyrosine hydroxylase (TH), a enzyme catalyzing the rate-limiting step in the synthesis of the neurotransmitter dopamine. Using molecular biological, biochemical and biophysical techniques we identified the C-terminal structured domain of PrP and the Nterminal regulatory domain of TH as interacting domains between these two proteins. This interaction does not affect TH activity in vitro, although co-expression experiments in HeLa and Chinese hamster ovary cells revealed that PrP is able to internalize TH. Moreover, TH modulated the level of expression of PrP and its localization at the plasma membrane. This novel interaction between two proteins of central importance in nervous system function may shed new light on our understanding of PrP in neurological diseases.
Keywords: Prion, tyrosine hydroxylase, protein-protein interaction, surface plasmon resonance.
CNS & Neurological Disorders - Drug Targets
Title:A Novel Prion Protein-Tyrosine Hydroxylase Interaction
Volume: 13 Issue: 5
Author(s): Mattia Vicario, Adriana Zagari, Vincenzo Granata, Francesca Munari, Stefano Mammi, Luigi Bubacco, Stephen D. Skaper and Alessandro Negro
Affiliation:
Keywords: Prion, tyrosine hydroxylase, protein-protein interaction, surface plasmon resonance.
Abstract: The prion protein (PrP) is currently one of the most studied molecules in the neurosciences. It is the main cause of a group of neurological diseases collectively called transmissible spongiform encephalopathies that severely affect both humans and a variety of mammals. Much effort has been directed to understanding the molecular basis of PrP activity, both in physiological and pathological terms. In this context, identification of neuronally-relevant interactors of PrP may play a crucial role. We recently discovered a specific, high-affinity (nanomolar KD) interaction with tyrosine hydroxylase (TH), a enzyme catalyzing the rate-limiting step in the synthesis of the neurotransmitter dopamine. Using molecular biological, biochemical and biophysical techniques we identified the C-terminal structured domain of PrP and the Nterminal regulatory domain of TH as interacting domains between these two proteins. This interaction does not affect TH activity in vitro, although co-expression experiments in HeLa and Chinese hamster ovary cells revealed that PrP is able to internalize TH. Moreover, TH modulated the level of expression of PrP and its localization at the plasma membrane. This novel interaction between two proteins of central importance in nervous system function may shed new light on our understanding of PrP in neurological diseases.
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Vicario Mattia, Zagari Adriana, Granata Vincenzo, Munari Francesca, Mammi Stefano, Bubacco Luigi, Skaper D. Stephen and Negro Alessandro, A Novel Prion Protein-Tyrosine Hydroxylase Interaction, CNS & Neurological Disorders - Drug Targets 2014; 13 (5) . https://dx.doi.org/10.2174/1871527313666140711092955
DOI https://dx.doi.org/10.2174/1871527313666140711092955 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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