Details

Autor(en) / Beteiligte

• Lea, Wendy A
• Winklhofer, Thomas
• Zelenchuk, Lesya
• Sharma, Madhulika
• Rossol-Allison, Jessica
• Fields, Timothy A
• Reif, Gail
• Calvet, James P
• Bakeberg, Jason L
• Wallace, Darren P
• Ward, Christopher J

Titel

Polycystin-1 Interacting Protein-1

Ist Teil von

• Cells (Basel, Switzerland), 2023-08, Vol.12 (17)

Ort / Verlag

MDPI AG

Erscheinungsjahr

2023

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The PKD1 gene, encoding protein polycystin-1 (PC1), is responsible for 85% of cases of autosomal dominant polycystic kidney disease (ADPKD). PC1 has been shown to be present in urinary exosome−like vesicles (PKD−ELVs) and lowered in individuals with germline PKD1 mutations. A label−free mass spectrometry comparison of urinary PKD−ELVs from normal individuals and those with PKD1 mutations showed that several proteins were reduced to a degree that matched the decrease observed in PC1 levels. Some of these proteins, such as polycystin-2 (PC2), may be present in a higher-order multi-protein assembly with PC1—the polycystin complex (PCC). CU062 (Q9NYP8) is decreased in ADPKD PKD−ELVs and, thus, is a candidate PCC component. CU062 is a small glycoprotein with a signal peptide but no transmembrane domain and can oligomerize with itself and interact with PC1. We investigated the localization of CU062 together with PC1 and PC2 using immunofluorescence (IF). In nonconfluent cells, all three proteins were localized in close proximity to focal adhesions (FAs), retraction fibers (RFs), and RF-associated extracellular vesicles (migrasomes). In confluent cells, primary cilia had PC1/PC2/CU062 + extracellular vesicles adherent to their plasma membrane. In cells exposed to mitochondrion-decoupling agents, we detected the development of novel PC1/CU062 + ring-like structures that entrained swollen mitochondria. In contact-inhibited cells under mitochondrial stress, PC1, PC2, and CU062 were observed on large, apically budding extracellular vesicles, where the proteins formed a reticular network on the membrane. CU062 interacts with PC1 and may have a role in the identification of senescent mitochondria and their extrusion in extracellular vesicles.