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Cited by 0Protein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase SignalingHippo pathway signaling and YAP/TAZ

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ASPPs multimerize protein phosphatase 1

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Wei, Derek T., Morrison, Kayleigh N., Beacham, Gwendolyn M., Beyrent, Erika, Habas, Cyrus A., Zhang, Ying, Florens, Laurence, Hollopeter, Gunther·2025·PLOS Genetics
DOI 10.1371/journal.pgen.1011731PMC PMC12543280

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Abstract

Protein Phosphatase 1 (PP1) activity is thought to be spatiotemporally defined by hundreds of different regulatory subunits, but their mechanisms of action are largely unknown. The Ankyrin repeat, SH3-domain, and Proline-rich region containing Proteins (ASPPs) bind and localize PP1 to cell-cell junctions. Here, we show ASPPs bind superstoichiometric amounts of PP1. Missense mutations in the ankyrin repeats of ASPPs, that were previously isolated from a forward genetic screen in Caenorhabditis elegans , reduce the stoichiometry of PP1 binding. Forcing PP1 oligomerization restores mutant ASPP function in vivo . We propose that ASPPs multimerize PP1 to establish a concentrated hub of phosphatase activity at cell-cell junctions.

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Metadata

Authors
Wei, D. T., Morrison, K. N., Beacham, G. M., Beyrent, E., Habas, C. A., Zhang, Y., Florens, L., & Hollopeter, G.
Affiliations
  • Cornell University (US)
  • Stowers Institute for Medical Research (US)
Corresponding author
Hollopeter, Gunther
ORCID
Venue
PLOS Genetics
Publisher
Public Library of Science (PLoS)
Published
2025-10-16
Volume
21
Issue
10
Pages
e1011731
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
DOI
10.1371/journal.pgen.1011731
PMC
PMC12543280
OpenAlex
W4415256892
Cited by
0
References
2
FWCI
0.00
Type
journal article
Language
en
Update notices
new_version (2025-10-22)
Open access
Licence
Locations
  • PLoS Genetics (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute of General Medical Sciences (R01GM127548, R35GM156633)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
Keywords
protein phosphatase 1, ASPP, ankyrin repeats, protein oligomerization, cell-cell contact, regulatory subunit, missense mutations, Caenorhabditis elegans

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