The RET51/FKBP52 complex and its involvement in Parkinson disease

Daniela Fusco, Manuela Vargiolu, Michele Vidone, Elisa Mariani, Lucia Fiammetta Pennisi, Elena Bonora, Sabina Capellari, Dietmar Dirnberger, Ralf Baumeister, Paolo Martinelli, Giovanni Romeo

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article numberddq181
Pages (from-to)2804-2816
Number of pages13
JournalHuman Molecular Genetics
Volume19
Issue number14
DOIs
Publication statusPublished - May 4 2010

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology
  • Medicine(all)

Cite this

Fusco, D., Vargiolu, M., Vidone, M., Mariani, E., Pennisi, L. F., Bonora, E., Capellari, S., Dirnberger, D., Baumeister, R., Martinelli, P., & Romeo, G. (2010). The RET51/FKBP52 complex and its involvement in Parkinson disease. Human Molecular Genetics, 19(14), 2804-2816. [ddq181]. https://doi.org/10.1093/hmg/ddq181