Basolateral protein Scribble binds phosphatase PP1 to establish a signaling network maintaining apicobasal polarity
| Autor: | Regina B. Troyanovsky, Sergey M. Troyanovsky, Rei Kato, Indrajyoti Indra, Brian J. Mitchell |
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| Rok vydání: | 2021 |
| Předmět: |
Protein family
Phosphatase Regulator Leucine-rich repeat ABP apicobasal polarity Biochemistry Cell Line Scribble GEF guanine nucleotide exchange factor chemistry.chemical_compound Protein Domains Cell cortex Humans Molecular Biology Tumor Suppressor Proteins fungi Cell Polarity Membrane Proteins BN-PAGE blue native–polyacrylamide gel electrophoresis Epithelial Cells Cell Biology basolateral polarity proteins PP1 phosphatase 1 phosphatase PP1 SBP streptavidin-binding peptide LAP leucine-rich repeat and PDZ domain Cell biology Receptors Neuropeptide Y LRR leucine-rich repeat TJ tight junction chemistry SBP-tag Guanine nucleotide exchange factor apicobasal polarity Protein Multimerization Protein ligand Protein Binding Signal Transduction Research Article |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X |
| Popis: | Scribble, a member of the LAP protein family, contributes to the apicobasal polarity (ABP) of epithelial cells. The LAP-unique region of these proteins, which is essential and sufficient for ABP, includes a conserved Leucine-Rich Repeat (LRR) domain. The major binding partners of this region that could regulate ABP remain unknown. Here, using proteomics, native gel electrophoresis, and site-directed mutagenesis, we show that the concave surface of LRR domain in Scribble participates in three types of mutually exclusive interactions—(i) homodimerization, serving as an auto-inhibitory mechanism; (ii) interactions with a diverse set of polarity proteins, such as Llgl1, Llgl2, EPB41L2, and EPB41L5, which produce distinct multiprotein complexes; and (iii) a direct interaction with the protein phosphatase, PP1. Analogy with the complex between PP1 and LRR domain of SDS22, a well-studied PP1 regulator, suggests that the Scibble-PP1 complex stores a latent form of PP1 in the basolateral cell cortex. Such organization may generate a dynamic signaling network wherein PP1 could be dispatched from the complex with Scribble to particular protein ligands, achieving fast dephosphorylation kinetics. |
| Databáze: | OpenAIRE |
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