Correlation between synaptogenesis and the PTEN phosphatase expression in dendrites during postnatal brain development.
The PTEN (phosphatase and tensin homolog deleted on chromosome 10) tumor suppressor gene codifies a lipid inositol 3'-phosphatase that negatively regulates cell survival mediated by the phosphatidyl inositol 3' kinase (PIP3-kinase)--protein kinase B/Akt signaling pathway. Recently, PIP3-kinase was involved in axon polarization, but PTEN functions in dendrites are uncertain. Using amino-terminal antibodies against the catalytic domain, we found a 34 kDa fragment of PTEN protein detected only in mouse brain tissue, present in neuron dendrites and spines of cerebral cortex, cerebellum, hippocampus and olfactory bulb. The PTEN-fragment reaches the synaptic fraction with a positive temporal correlation with synaptic stabilization in postnatal cerebellum and brain. In the weaver mutant mice, PTEN was absent only in the Purkinje cells dendrites that cannot receive the granule cells synaptic input. Furthermore, the activated p-Akt/PKB was present in axons but not in dendrites of mature neuron cells. P-Akt was also altered by the weaver mutation maintaining the inverse correlation with the PTEN-fragment in Purkinje cell dendrites. In contrast, the expression of this fragment was not affected by the staggerer mutation. Together, these results suggest that synaptogenesis is a necessary process for polarization in PIP3 pathway mediated by the PTEN catalytic-fragment into dendrites of CNS neurons.
Perandones
Claudia
C
Fundación Instituto Leloir, (IIBBA-CONICET, IIB-FCEN-UBA), Avenue Patricias Argentinas 435, Buenos Aires 1405, Argentina.
Costanzo
Roxana Verónica
RV
Kowaljow
Valeria
V
Pivetta
Omar Hilario
OH
Carminatti
Hector
H
Radrizzani
Martín
M
D000818:Animals; D001921:Brain / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D020134:Catalytic Domain; D016764:Cell Polarity; D003712:Dendrites / Q000201:enzymology* / Q000648:ultrastructure; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D051059:PTEN Phosphohydrolase; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000502:physiology; D013223:Statistics as Topic; D013569:Synapses / Q000502:physiology*; D014018:Tissue Distribution; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D051059:PTEN Phosphohydrolase; D010446:Peptide Fragments; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D025521:Tumor Suppressor Proteins; C487757:Pten protein, mouse