RGD Reference Report - Selective targeting of the gamma1 isoform of protein phosphatase 1 to F-actin in intact cells requires multiple domains in spinophilin and neurabin. - Rat Genome Database

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Selective targeting of the gamma1 isoform of protein phosphatase 1 to F-actin in intact cells requires multiple domains in spinophilin and neurabin.

Authors: Carmody, LC  Baucum AJ, 2ND  Bass, MA  Colbran, RJ 
Citation: Carmody LC, etal., FASEB J. 2008 Jun;22(6):1660-71. doi: 10.1096/fj.07-092841. Epub 2008 Jan 23.
RGD ID: 8554111
Pubmed: (View Article at PubMed) PMID:18216290
DOI: Full-text: DOI:10.1096/fj.07-092841

Protein phosphatase 1 (PP1) catalytic subunits dephosphorylate specific substrates in discrete subcellular compartments to modulate many cellular processes. Canonical PP1-binding motifs (R/K-V/I-X-F) in a family of proteins mediate subcellular targeting, and the amino acids that form the binding pocket for the canonical motif are identical in all PP1 isoforms. However, PP1gamma1 but not PP1beta is selectively localized to F-actin-rich dendritic spines in neurons. Although the F-actin-binding proteins neurabin I and spinophilin (neurabin II) also bind PP1, their role in PP1 isoform selective targeting in intact cells is poorly understood. We show here that spinophilin selectively targets PP1gamma1, but not PP1beta, to F-actin-rich cortical regions of intact cells. Mutation of a PP1gamma1 selectivity determinant (N(464)EDYDRR(470) in spinophilin: conserved as residues 473-479 in neurabin) to VKDYDTW severely attenuated PP1gamma1 interactions with neurabins in vitro and in cells and disrupted PP1gamma1 targeting to F-actin. This domain is not involved in the weaker interactions of neurabins with PP1beta. In contrast, mutation of the canonical PP1-binding motif attenuated interactions of neurabins with both isoforms. Thus, selective targeting of PP1gamma1 to F-actin by neurabins in intact cells requires both the canonical PP1-binding motif and an auxiliary PP1gamma1-selectivity determinant.

Annotation

Gene Ontology Annotations    

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Ppp1cb  (protein phosphatase 1 catalytic subunit beta)
Ppp1cc  (protein phosphatase 1 catalytic subunit gamma)
Ppp1r9a  (protein phosphatase 1, regulatory subunit 9A)
Ppp1r9b  (protein phosphatase 1, regulatory subunit 9B)


Additional Information