Periphilin is a novel interactor of synphilin-1, a protein  implicated in Parkinson's disease.
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons and the presence of Lewy bodies. Alpha-synuclein and its interactor synphilin-1 are major components of these inclusions. Rare mutations in the alpha-synuclein and synphilin-1 genes have been implicated in the pathogenesis of PD; however, the normal function of these proteins is far from being completely elucidated. We, thus, searched for novel synphilin-1-interacting proteins and deciphered periphilin as new interactor. Periphilin isoforms are involved in multiple cellular functions in vivo, and the protein is broadly expressed during embryogenesis and in the adult brain. We show that periphilin displays an overlapping expression pattern with synphilin-1 in cellular and animal models and in Lewy bodies of PD patients. Functional studies demonstrate that periphilin, as previously shown for synphilin-1, displays an antiapoptotic function by reducing caspase-3 activity. Searching for mutations in the periphilin gene, we detected a K69E substitution in two patients of a PD family. Taken together, these findings support for the first time an involvement of periphilin in PD.
Soehn
Anne S
AS
Department of Medical Genetics, University of Tuebingen, Tuebingen, Germany. anne.soehn@med.uni-tuebingen.de
Franck
Thomas
T
Biskup
Saskia
S
Giaime
Emilie
E
Melle
Christian
C
Rott
Ruth
R
Cebo
Daniel
D
Kalbacher
Hubert
H
Ott
Erwin
E
Pahnke
Jens
J
Meitinger
Thomas
T
Krüger
Rejko
R
Gasser
Thomas
T
Berg
Daniela
D
von Eggeling
Ferdinand
F
Engelender
Simone
S
da Costa
Cristine Alves
CA
Riess
Olaf
O
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004252:DNA Mutational Analysis; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques
D000951:Antigens, Neoplasm; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C478775:PPHLN1 protein, human; C118958:SNCAIP protein, human