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PICK1 interacts with and attenuates PAEL receptor-mediated cell death

Dutta, Priyanka and O'Connell, Kara and Ozkan, S. Banu and Sailer, Andreas and Dev, Kumlesh K. (2014) PICK1 interacts with and attenuates PAEL receptor-mediated cell death. Journal of Neurochemistry, 130. pp. 360-373.

Abstract

The parkin-associated endothelial-like
receptor (PAELR) is an orphan G protein-coupled
receptor (GPCR), initially named as GPR37. This
receptor interacts with parkin and is degraded by
parkin-mediated ubiquitination. Mutations in
parkin are thought to result in PAELR
accumulation and neuronal death in Parkinson’s
disease. Here we aimed to identify proteins that
interact with and regulate expression levels of the
PAELR. In this study, we report that the protein
interacting with C-kinase (PICK1) interacts with
PAELR. Specifically, the PSD-95/Discs large/ZO-1
(PDZ) domain of PICK1 was shown to interact with
the extreme c-terminal (ct) located PDZ motif of
PAELR. Pull-down assays indicated that
recombinant and native PICK1, obtained from
heterologous cells and rat brain tissue, respectively,
were retained by a glutathione S-transferase fusion
of ct-PAELR. PICK1 has previously been shown to
bind parkin and PAELR is known to be degraded by
parkin-mediated ubiquitination. We show that
PICK1 wildtype caused a reduction in PAELR
expression levels in transiently transfected
heterologous cells compared to a PICK1 PDZ
domain mutant, which does not interact with
PAELR. Finally, PICK1 overexpression in HEK293
cells attenuated cell viability induced by PAEALR
overexpression during rotenone treatment. These
results suggest a role for PICK1 in preventing
PAELR-induced cell toxicity during conditions of
cell stress.

Item Type: Article
Keywords: Protein interacting with C Kinase (PICK1); Parkin-associated endothelial-like receptor (PAEL receptor), GPR37, Parkinson’s disease (PD)
Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14
URI: https://oak.novartis.com/id/eprint/6141

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