Basolateral Protein Scribble Provides Phosphatase PP1 to a Signaling Network Maintaining Apicobasal Polarity
Ontology highlight
ABSTRACT:
INSTRUMENT(S): LTQ Orbitrap Elite
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Sergey M Troyanovsky
PROVIDER: MSV000088094 | MassIVE |
SECONDARY ACCESSION(S): PXD028463
REPOSITORIES: MassIVE
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Project description: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.
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