Basolateral protein Scribble binds phosphatase PP1 to establish a signaling network maintaining apicobasal polarity

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 co...

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Bibliographic Details
Published in:The Journal of biological chemistry 2021-11, Vol.297 (5), p.101289, Article 101289
Main Authors: Troyanovsky, Regina B., Indra, Indrajyoti, Kato, Rei, Mitchell, Brian J., Troyanovsky, Sergey M.
Format: Article
Language:English
Subjects:
apicobasal polarity
basolateral polarity proteins
Cell Line
Cell Polarity
Epithelial Cells - metabolism
Humans
Membrane Proteins - chemistry
Membrane Proteins - genetics
Membrane Proteins - metabolism
phosphatase PP1
Protein Binding
Protein Domains
Protein Multimerization
Receptors, Neuropeptide Y - chemistry
Receptors, Neuropeptide Y - genetics
Receptors, Neuropeptide Y - metabolism
Scribble
Signal Transduction
Tumor Suppressor Proteins - chemistry
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1016/j.jbc.2021.101289