Anp32e/Cpd1 regulates protein phosphatase 2A activity at synapses during synaptogenesis

• Published in: The European journal of neuroscience 2006-01, Vol.23 (2), p.309-324
• Main Authors: Costanzo, Roxana V., Vilá-Ortíz, Guillermo J., Perandones, Claudia, Carminatti, Héctor, Matilla, Antoni, Radrizzani, Martín
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Animals, Newborn; Anp32e; Blotting, Western - methods; Brain - cytology; Brain - growth & development; Brain - metabolism; Gene Expression Regulation, Developmental - physiology; Immunohistochemistry - methods; Mice; Mice, Inbred C57BL; Mice, Neurologic Mutants; Microscopy, Immunoelectron - methods; Molecular Weight; Nerve Tissue Proteins - physiology; Organogenesis; Phosphoprotein Phosphatases - metabolism; Protein Isoforms - metabolism; Protein Phosphatase 2; protein phosphatase 2A; Subcellular Fractions - metabolism; Subcellular Fractions - ultrastructure; Synapses - metabolism; Synapses - ultrastructure; synapses formation; vesicle transport
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2005.04555.x

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.