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Anp32e/Cpd1 regulates protein phosphatase 2A activity at synapses during synaptogenesis.
- Source :
-
The European journal of neuroscience [Eur J Neurosci] 2006 Jan; Vol. 23 (2), pp. 309-24. - Publication Year :
- 2006
-
Abstract
- Anp32e/Cpd1, a member of the acidic nuclear phosphoprotein (Anp)32 family, is characterized by the presence of an amino terminal domain containing four leucine-rich repeats and a carboxyl-terminal low-compositional complexity acidic region. In previous studies performed to understand the biological role of Anp32e/Cpd1, we showed a predominant presence of Anp32e/Cpd1 in the nucleus. However, when Anp32e/Cpd1 is in the cytoplasm, it co-localizes spatially with protein phosphatase 2A (PP2A) near cell membranes, far from the synapses. In the present work, we show that Anp32e/Cpd1 is also present as a membrane-bound 74/76-kDa protein with a widespread distribution in the brain. We reveal that the expression, synthesis and half-life of this high-molecular-weight form of Anp32e/Cpd1 are spatially and temporally correlated with the cerebellar synaptogenesis period. We demonstrate that synaptic Anp32e/Cpd1 co-localizes, interacts and inhibits PP2A activity, and that phosphorylation of Anp32/Cpd1 is required for the Anp32e-PP2A interaction. Also, subcellular localization was shown with electronic microscopy. Finally, we examine Anp32e/Cpd1 and PP2A distribution in two ataxic mutant models, weaver and staggerer, and show that their co-localization in Purkinje cell dendrites depends on parallel fibre/Purkinje cell contacts. Based on these observations, we propose that Anp32e/Cpd1 mediates synaptogenesis process by modulating PP2A activity.
- Subjects :
- Age Factors
Animals
Animals, Newborn
Blotting, Western methods
Brain cytology
Brain metabolism
Immunohistochemistry methods
Mice
Mice, Inbred C57BL
Mice, Neurologic Mutants
Microscopy, Immunoelectron methods
Molecular Chaperones
Molecular Weight
Organogenesis
Protein Isoforms metabolism
Protein Phosphatase 2
Subcellular Fractions metabolism
Subcellular Fractions ultrastructure
Synapses ultrastructure
Brain growth & development
Gene Expression Regulation, Developmental physiology
Nerve Tissue Proteins physiology
Phosphoprotein Phosphatases metabolism
Synapses metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0953-816X
- Volume :
- 23
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The European journal of neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 16420440
- Full Text :
- https://doi.org/10.1111/j.1460-9568.2005.04555.x