The compartmentalized domains of polarized epithelial cells arise from mutually antagonistic actions between the apical Par complex and the basolateral Scrib module. In Drosophila, the Scrib module proteins Scribble (Scrib) and Discs-large (Dlg) are required to limit Lgl phosphorylation at the basolateral cortex, but how Scrib and Dlg could carry out such a 'protection' activity is not clear. We tested Protein Phosphatase 1α (PP1) as a potential mediator of this activity, but demonstrate that a significant component of Scrib and Dlg regulation of Lgl is PP1 independent, and found no evidence for a Scrib-Dlg-PP1 protein complex. However, the Dlg SH3 domain plays a role in Lgl protection and, in combination with the N-terminal region of the Dlg HOOK domain, in recruitment of Scrib to the membrane. We identify a 'minimal Dlg' comprised of the SH3 and HOOK domains that is both necessary and sufficient for Scrib localization and epithelial polarity function in vivo. This article has an associated First Person interview with the first author of the paper.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346270 | PMC |
| http://dx.doi.org/10.1242/bio.059408 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Planar cell polarity regulators in asymmetric organogenesis during development and disease.
J Genet Genomics
February 2023
Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China; Laboratory of Developmental Biology, CNRS-UMR7622, Institut de Biologie Paris-Seine (IBPS), Sorbonne University, 75005 Paris, France. Electronic address:
The phenomenon of planar cell polarity is critically required for a myriad of morphogenetic processes in metazoan and is accurately controlled by several conserved modules. Six "core" proteins, including Frizzled, Flamingo (Celsr), Van Gogh (Vangl), Dishevelled, Prickle, and Diego (Ankrd6), are major components of the Wnt/planar cell polarity pathway. The Fat/Dchs protocadherins and the Scrib polarity complex also function to instruct cellular polarization.
View Article and Find Full Text PDFMinimal functional domains of the core polarity regulator Dlg.
Biol Open
July 2022
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
The compartmentalized domains of polarized epithelial cells arise from mutually antagonistic actions between the apical Par complex and the basolateral Scrib module. In Drosophila, the Scrib module proteins Scribble (Scrib) and Discs-large (Dlg) are required to limit Lgl phosphorylation at the basolateral cortex, but how Scrib and Dlg could carry out such a 'protection' activity is not clear. We tested Protein Phosphatase 1α (PP1) as a potential mediator of this activity, but demonstrate that a significant component of Scrib and Dlg regulation of Lgl is PP1 independent, and found no evidence for a Scrib-Dlg-PP1 protein complex.
View Article and Find Full Text PDFDesigning of disruptor molecules to restrain the protein-protein interaction network of VANG1/SCRIB/NOS1AP using fragment-based drug discovery techniques.
Mol Divers
June 2023
Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, 39, India.
Governing protein-protein interaction networks are the cynosure of cell signaling and oncogenic networks. Multifarious processes when aligned with one another can result in a dysregulated output which can result in cancer progression. In the current research, one such network of proteins comprising VANG1/SCRIB/NOS1AP, which is responsible for cell migration, is targeted.
View Article and Find Full Text PDFStructural Basis of the Avian Influenza NS1 Protein Interactions with the Cell Polarity Regulator Scribble.
Viruses
March 2022
Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
Article Synopsis
- Scribble is crucial for cell polarity, working with proteins like Disc-large and Lethal-2-giant larvae to maintain cellular asymmetry; disruptions are linked to worse outcomes in viral infections.
- Viruses, particularly the influenza A virus, target Scribble's PDZ domains to disrupt normal cell function, notably the binding of the virus's NS1 protein to Scribble.
- Recent research revealed specific binding interactions between different NS1 protein motifs and Scribble's PDZ domains, enhancing our understanding of how influenza A virus affects cell polarity and disease development.
Plakophilin 3 and Par3 facilitate desmosomes' association with the apical junctional complex.
Mol Biol Cell
September 2021
Departments of Dermatology and Cell & Molecular Biology and.
Desmosomes (DSMs), together with adherens junctions (AJs) and tight junctions (TJs), constitute the apical cell junctional complex (AJC). While the importance of the apical and basolateral polarity machinery in the organization of AJs and TJs is well established, how DSMs are positioned within the AJC is not understood. Here we use highly polarized DLD1 cells as a model to address how DSMs integrate into the AJC.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!