RGD Reference Report - The neuronal actin-binding proteins, neurabin I and neurabin II, recruit specific isoforms of protein phosphatase-1 catalytic subunits. - Rat Genome Database

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The neuronal actin-binding proteins, neurabin I and neurabin II, recruit specific isoforms of protein phosphatase-1 catalytic subunits.

Authors: Terry-Lorenzo, RT  Carmody, LC  Voltz, JW  Connor, JH  Li, S  Smith, FD  Milgram, SL  Colbran, RJ  Shenolikar, S 
Citation: Terry-Lorenzo RT, etal., J Biol Chem 2002 Aug 2;277(31):27716-24.
RGD ID: 625568
Pubmed: PMID:12016225   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M203365200   (Journal Full-text)

Neurabins are protein phosphatase-1 (PP1) targeting subunits that are highly concentrated in dendritic spines and post-synaptic densities. Immunoprecipitation of neurabin I and neurabin II/spinophilin from rat brain extracts sedimented PP1gamma1 and PP1alpha but not PP1beta. In vitro studies showed that recombinant peptides representing central regions of neurabins also preferentially bound PP1gamma1 and PP1alpha from brain extracts and associated poorly with PP1beta. Analysis of PP1 binding to chimeric neurabins suggested that sequences flanking a conserved PP1-binding motif altered their selectivity for PP1beta and their activity as regulators of PP1 in vitro. Assays using recombinant PP1 catalytic subunits and a chimera of PP1 and protein phosphatase-2A indicated that the C-terminal sequences unique to the PP1 isoforms contributed to their recognition by neurabins. Collectively, the results from several different in vitro assays established the rank order of PP1 isoform selection by neurabins to be PP1gamma1 > PP1alpha > PP1beta. This PP1 isoform selectivity was confirmed by immunoprecipitation of neurabin I and II from brain extracts from wild type and mutant PP1gamma null mice. In the absence of PP1gamma1, both neurabins showed enhanced association with PP1alpha but not PP1beta. These studies identified some of the structural determinants in PP1 and neurabins that together contribute to preferential targeting of PP1gamma1 and PP1alpha to the mammalian synapse.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of phosphoprotein phosphatase activity  IDA 625568 RGD 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Ppp1ca  (protein phosphatase 1 catalytic subunit alpha)
Ppp1r9a  (protein phosphatase 1, regulatory subunit 9A)
Ppp1r9b  (protein phosphatase 1, regulatory subunit 9B)

Objects referenced in this article
Gene Ppp1cc protein phosphatase 1 catalytic subunit gamma Rattus norvegicus

Additional Information