Differential cellular and subcellular localization of protein phosphatase 1 isoforms in brain

✍ Scribed by Strack, Stefan; Kini, Sunil; Ebner, Ford F.; Wadzinski, Brian E.; Colbran, Roger J.

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 798 KB
• Volume: 413
• Category: Article
• ISSN: 0021-9967
• DOI: 10.1002/(sici)1096-9861(19991025)413:3<373::aid-cne2>3.0.co;2-z

✦ Synopsis

Protein phosphatase 1 (PP1) is a gene family with a number of important functions in brain. Association with a wide variety of regulatory/targeting subunits is thought to be instrumental in directing the phosphatase to specific subcellular locations and substrates. By using antibodies directed against specific PP1 isoforms, we asked whether PP1 isoforms are differentially distributed in brain. Immunoblotting detects in brain the PP1␥2 isoform, which had previously been thought to be testis specific, in addition to ␣, ␤, and ␥1 isoforms. PP1 isoform expression varies modestly in extracts from different subdissected brain regions and is relatively constant during postnatal development, except for an about twofold increase in PP1␥2. By immunohistochemical analyses of rat brain, PP1␤ and PP1␥1 cellular expression is widespread but quite distinct from one another. Subcellular fractionation studies demonstrate that PP1␤ and PP1␥1 are selectively associated with different cytoskeletal elements: PP1␤ with microtubules, PP1␥1 with the actin cytoskeleton. Double-immunofluorescence labeling of cultured cortical neurons further reveals a strikingly different and nonoverlapping localization of PP1␤ and PP1␥1: whereas PP1␤ localizes to a discrete area of the soma, PP1␥1 is highly enriched in dendritic spines and presynaptic terminals of cultured neurons. These results show that PP1 isoforms are targeted to different neuronal cytoskeletal compartments with a high degree of specificity, presumably by isoform-specific association with regulatory/ targeting proteins. Furthermore, the synaptic localization of PP1␥1 indicates that it is this isoform that is involved in the regulation of synaptic phosphoproteins such as neurotransmitter receptors and ion channels implicated in synaptic plasticity.