Dataset Information

Basolateral Protein Scribble Provides Phosphatase PP1 to a Signaling Network Maintaining Apicobasal Polarity

ABSTRACT: Scribble, a member of the LAP protein family, contributes to the apicobasal polarity (ABP) of epithelial cells. The LAP unique region (LUR) of these proteins is essential for ABP function, and includes a highly conserved Leucine Reach Repeat (LRR) domain. Here we study how the LRR domain of Scribble maintains ABP. We show that its concave surface participates in three types of mutually exclusive interactions 1. homodimerization serving as an auto-inhibitory mechanism, 2. interactions with a diverse set of polarity proteins, such as Llgl1, Llgl2, EPB41L2 and EPB41L5, which produce distinct multiprotein complexes, and 3. a direct interaction with the protein phosphatase, PP1, which forms a dimeric LRR domain-PP1 complex. Our results suggest that the latter complex maintains PP1 in the basolateral cell cortex in close proximity to PP1 targets. Such organization generates a dynamic network where PP1 could be immediately dispatched from the Scribble-PP1 complex to particular protein ligands. This mechanism for controlling dephosphorylation kinetics of phosphorylated proteins could be universal for all members of the LAP protein family, which includes Erbin, Lano, and the neuron-specific protein, Densin-180.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Colon

DISEASE(S): Colon Cancer

SUBMITTER: Indrajyoti Indra

LAB HEAD: Sergey Troyanovsky

PROVIDER: PXD028919 | Pride | 2021-11-03

REPOSITORIES: Pride

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			Action	DRS
	20190213_maz683_19-1589_Troyanovsky_1.raw	Raw
	20190213_maz683_19-1589_Troyanovsky_1__F022899_.mzid.gz	Mzid
	20190213_maz683_19-1589_Troyanovsky_1__F022899_.mzid_20190213_maz683_19-1589_Troyanovsky_1__F022899_.MGF	Mzid
	20190228_vcs075_19-1606_Troyanovsky_Sample01.raw	Raw
	20190228_vcs075_19-1606_Troyanovsky_Sample01__F022990_.mzid.gz	Mzid

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Publications

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

Troyanovsky Regina B RB Indra Indrajyoti I Kato Rei R Mitchell Brian J BJ Troyanovsky Sergey M SM

The Journal of biological chemistry 20211008 5

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 typ ...[more]

PMID: 34634305

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