The RET51/FKBP52 complex and its involvement in Parkinson disease
| Autor: | Elena Bonora, Manuela Vargiolu, Lucia Fiammetta Pennisi, Dietmar Dirnberger, Ralf Baumeister, Paolo Martinelli, Daniela Fusco, Sabina Capellari, Elisa Mariani, Michele Vidone, Giovanni Romeo |
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| Přispěvatelé: | Fusco D, Vargiolu M, Vidone M, Mariani E, Pennisi LF, Bonora E, Capellari S, Dirnberger D, Baumeister R, Martinelli P, Romeo G. |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male medicine.medical_specialty Models Biological Neuroprotection Receptor tyrosine kinase Cell Line Tacrolimus Binding Proteins Young Adult Neurotrophic factors Internal medicine Nerve Growth Factor Protein Interaction Mapping Genetics medicine Glial cell line-derived neurotrophic factor Humans Protein Interaction Domains and Motifs Genetic Testing Glial Cell Line-Derived Neurotrophic Factor Phosphorylation Tyrosine Molecular Biology Genetic Association Studies Genetics (clinical) Peptidylprolyl isomerase biology Proto-Oncogene Proteins c-ret RET51 Parkinson Disease General Medicine Middle Aged FKBP52 Cell biology Endocrinology nervous system Multiprotein Complexes biology.protein Female Protein Kinases GDNF family of ligands PARKINSON'S DISEASE Protein Binding |
| Popis: | The tyrosine kinase receptor RET51 is expressed in distinct families of neurons where it promotes different functions. FKBP52 is an immunophilin with neuroprotective effects on different kinds of neurons. In this paper, we demonstrate that RET51 activation by both glial cell line-derived neurotrophic factor (GDNF) and NGF triggers the formation of RET51/FKBP52 complex. The substitution of the tyrosine 905 of RET51, a key residue phosphorylated by both GDNF and NGF, disrupts the RET51/FKBP52 complex. NGF and GDNF have a functional role in dopaminergic (DA) neurons where RET51 and FKBP52 are expressed with a yet undefined function. To clarify if RET51/FKBP52 complex should exert its function in DA neurons, we used an indirect approach by screening the genes encoding for RET51 and FKBP52 in a group of 30 Parkinson's disease patients. The degeneration of DA neurons is the main feature of PD, which is associated to a complex multifactorial aetiology combining environmental, age-related and genetic factors. We found a compound heterozygous carrying two mutations in RET and FKBP52 that are sufficient to disrupt the RET51/FKBP52 complex, indicating its potential role in PD. |
| Databáze: | OpenAIRE |
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