The parkin-associated endothelial-like receptor (PAELR, GPR37) is an orphan G protein-coupled receptor that interacts with and is degraded by parkin-mediated ubiquitination. Mutations in parkin are thought to result in PAELR accumulation and increase neuronal cell death in Parkinson's disease. In this study, we find that the protein interacting with C-kinase (PICK1) interacts with PAELR. Specifically, the Postsynaptic density protein-95/Discs large/ZO-1 (PDZ) domain of PICK1 interacted with the last three residues of the 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. Furthermore, coimmunoprecipitation studies isolated a PAELR-PICK1 complex from transiently transfected cells. PICK1 interacts with parkin and our data showed that PICK1 reduces PAELR expression levels in transiently transfected heterologous cells compared to a PICK1 mutant that does not interact with PAELR. Finally, PICK1 over-expression in HEK293 cells reduced cell death induced by PAEALR over-expression during rotenone treatment and these effects of PICK1 were attenuated during inhibition of the proteasome. These results suggest a role for PICK1 in preventing PAELR-induced cell toxicity.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1111/jnc.12741 | DOI Listing |
Biofactors
January 2025
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Tongji University, Shanghai, People's Republic of China.
Breast cancer continues to be a major health issue for women worldwide, with vimentin (VIM) identified as a crucial factor in its progression due to its role in cell migration and the epithelial-to-mesenchymal transition (EMT). This study focuses on elucidating VIM's regulatory mechanisms on the miR-615-3p/PICK1 axis. Utilizing the 4T1 breast cancer cell model, we first used RNA-seq and proteomics to investigate the changes in the APA of PICK1 following VIM knockout (KO).
View Article and Find Full Text PDFAnim Reprod
October 2024
College of Animal Science and Technology, Yunnan Agricultural University, Kunming, Yunnan, China.
Mol Biol Cell
October 2024
Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
The aggresome is a perinuclear structure that sequesters misfolded proteins. It is implicated in various neurodegenerative diseases. The perinuclear structure enriched with protein interacting with C kinase 1 (PICK1) was found to be inducible by cellular stressors, colocalizing with microtubule-organizing center markers and ubiquitin, hence classifying it as an aggresome.
View Article and Find Full Text PDFEur Heart J
August 2024
Cedars-Sinai Medical Center, Smidt Heart Institute, 8700 Beverly Blvd, 1090 Davis Bldg, Los Angeles, CA 90048, USA.
Background And Aims: Extracellular vesicles (EVs) secreted by cardiosphere-derived cells exert immunomodulatory effects through the transmission of small non-coding RNAs.
Methods: The mechanism and role of yREX3, a small Y RNA abundant in EVs in myocardial injury, was investigated.
Results: yREX3 attenuates cardiac ischaemic injury by selective DNA methylation.
ACS Chem Neurosci
May 2024
Depatment of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
PDZ domains are modular domains that conventionally bind to C terminal or internal motifs of target proteins to control cellular functions through the regulation of protein complex assemblies. Almost all reported structures of PDZ-target protein complexes rely on fragments or peptides as target proteins. No intact target protein complexed with PDZ was structurally characterized.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!