Journal article
Association of brain protein phosphatase 1 with cytoskeletal targeting/regulatory subunits
Journal of neurochemistry, Vol.69(3), pp.920-929
1997
DOI: 10.1046/j.1471-4159.1997.69030920.x
PMID: 9282913
Abstract
Protein phosphatase 1 catalytic subunit (PP1C) is highly enriched in isolated rat postsynaptic densities. Gel overlay analyses using digoxigenin (DIG)‐labeled PP1C revealed four major rat brain PP1C‐binding proteins (PP1bps) with molecular masses of ≈216, 175, 134, and 75 kDa, which were (1) more abundant in brain than other rat tissues; (2) differentially expressed in microdissected brain regions; and (3) enriched in isolated cortex postsynaptic densities. PP1bp175, PP1bp134, PP1bp75, and PP1C were partially released from forebrain particulate extracts by incubation at low ionic strength, which destabilizes the actin cytoskeleton. Size‐exclusion chromatography of solubilized extracts separated two main PP1 activities (≈600 and ≈100 kDa). PP1bps and PP1Cγ1 were enriched in the ≈600‐kDa peak, but PP1Cβ was enriched in the ≈100‐kDa peak. Furthermore, PP1bp175 and PP1bp134 exhibited lower binding of recombinant DIG‐PP1Cβ than recombinant DIG‐PP1Cγ1 or DIG‐PP1Cα. Solubilized PP1bp175 and PP1bp134 interact with PP1C under native conditions, because they both (1) coeluted from size‐exclusion and ion‐exchange columns; (2) bound to microcystin‐LR‐Sepharose; and (3) coprecipitated using PP1C antibodies. Trypsinolysis of the ≈600‐kDa form of PP1 increased phosphorylase a phosphatase activity approximately fourfold, suggesting that interaction of PP1C with these PP1bps modulates its activity. Thus, brain PP1 activity is likely targeted to the cytoskeleton, including postsynaptic densities, by isoform‐selective binding of PP1C to these targeting/regulatory subunits, contributing to the specificity of its physiological roles.
Details
- Title: Subtitle
- Association of brain protein phosphatase 1 with cytoskeletal targeting/regulatory subunits
- Creators
- Roger J Colbran - Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United StatesMartha A Bass - Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United StatesR Blair McNeill - Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United StatesMathieu Bollen - Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Leuven, BelgiumSumin Zhao - Department of Biochemistry, University of Miami School of Medicine, Miami, Florida, United StatesBrian E Wadzinski - Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, United StatesStefan Strack - Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States
- Resource Type
- Journal article
- Publication Details
- Journal of neurochemistry, Vol.69(3), pp.920-929
- Publisher
- Blackwell; Oxford
- DOI
- 10.1046/j.1471-4159.1997.69030920.x
- PMID
- 9282913
- ISSN
- 0022-3042
- eISSN
- 1471-4159
- Language
- English
- Date published
- 1997
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
- Record Identifier
- 9984040363102771
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