Format

Send to

Choose Destination
See comment in PubMed Commons below
FASEB J. 2008 Jun;22(6):1660-71. doi: 10.1096/fj.07-092841. Epub 2008 Jan 23.

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

Author information

  • 1Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

Abstract

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.

PMID:
18216290
PMCID:
PMC2814319
DOI:
10.1096/fj.07-092841
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center