NHERFs are the best-studied apical PDZ proteins that are highly expressed in epithelial cells. Molecular and cellular studies over the past decade show that NHERFs regulate the targeting or trafficking of ion transporters and other membrane proteins and transduce physiological and pathophysiological signals that regulate ion homeostasis in mammals.
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http://dx.doi.org/10.1152/physiol.00020.2004 | DOI Listing |
Biochem J
January 2025
University of Pittsburgh School of Medicine, Pittsburgh, United States.
The sodium phosphate cotransporter-2A (NPT2A) mediates basal and parathyroid hormone (PTH)- and fibroblast growth factor-23 (FGF23)-regulated phosphate transport in proximal tubule cells of the kidney. Both basal and hormone-sensitive transport require sodium hydrogen exchanger regulatory factor-1 (NHERF1), a scaffold protein with tandem PDZ domains, PDZ1 and PDZ2. NPT2A binds to PDZ1.
View Article and Find Full Text PDFFEBS J
January 2025
Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Canada.
In this study, we explored the intricate relationship between Pannexin 1 (PANX1) and the Hippo signaling pathway effector, Yes-associated protein (YAP). Analysis of The Cancer Genome Atlas (TCGA) data revealed a significant positive correlation between PANX1 mRNA and core Hippo components, Yes-associated protein 1 [YAP], Transcriptional coactivator with PDZ-binding motif [TAZ], and Hippo scaffold, Ras GTPase-activating-like protein IQGAP1 [IQGAP1], in invasive cutaneous melanoma and breast carcinoma. Furthermore, we demonstrated that PANX1 expression is upregulated in invasive melanoma cell lines and is associated with increased YAP protein levels.
View Article and Find Full Text PDFBone fracture repair initiates by periosteal expansion. The periosteum is typically quiescent, but upon fracture, periosteal cells proliferate and contribute to bone fracture repair. The expansion of the periosteum is regulated by gene transcription; however, the molecular mechanisms behind periosteal expansion are unclear.
View Article and Find Full Text PDFNat Struct Mol Biol
January 2025
Signalling and Structural Biology Laboratory, Francis Crick Institute, London, UK.
The mutually antagonistic relationship of atypical protein kinase C (aPKC) and partitioning-defective protein 6 (Par6) with the substrate lethal (2) giant larvae (Lgl) is essential for regulating polarity across many cell types. Although aPKC-Par6 phosphorylates Lgl at three serine sites to exclude it from the apical domain, aPKC-Par6 and Lgl paradoxically form a stable kinase-substrate complex, with conflicting roles proposed for Par6. We report the structure of human aPKCι-Par6α bound to full-length Llgl1, captured through an aPKCι docking site and a Par6 contact.
View Article and Find Full Text PDFElife
January 2025
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited.
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