Leptin Regulates AMPA Receptor Trafficking via PTEN Inhibition
| Autor: | Jenni Harvey, Sandra D. Santos, Andrew J. Irving, Ana Luísa Carvalho, Christopher N. Connolly, Yvonne E. Lindsay, Peter R. Moult, Nick R. Leslie, Alasdair Cross |
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| Rok vydání: | 2010 |
| Předmět: |
Leptin
Male medicine.medical_specialty Molecular Sequence Data AMPA receptor Hippocampal formation Neurotransmission Transfection Hippocampus Rats Sprague-Dawley Phosphatidylinositol Phosphates Internal medicine medicine Animals Humans PTEN Amino Acid Sequence Receptors AMPA Phosphorylation Cells Cultured biology General Neuroscience digestive oral and skin physiology PTEN Phosphohydrolase Long-term potentiation Rats Rats Zucker Protein Transport Endocrinology nervous system Synaptic plasticity biology.protein NMDA receptor hormones hormone substitutes and hormone antagonists |
| Zdroj: | The Journal of Neuroscience. 30:4088-4101 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | The hormone leptin can cross the blood–brain barrier and influences numerous brain functions (Harvey, 2007). Indeed, recent studies have demonstrated that leptin regulates activity-dependent synaptic plasticity in the CA1 region of the hippocampus (Shanley et al., 2001; Li et al., 2002; Durakoglugil et al., 2005; Moult et al., 2009). It is well documented that trafficking of AMPA receptors is pivotal for hippocampal synaptic plasticity (Collingridge et al., 2004), but there is limited knowledge of how hormonal systems like leptin influence this process. In this study we have examined how leptin influences AMPA receptor trafficking and in turn how this impacts on excitatory synaptic function. Here we show that leptin preferentially increases the cell surface expression of GluR1 and the synaptic density of GluR2-lacking AMPA receptors in adult hippocampal slices. The leptin-induced increase in surface GluR1 required NMDA receptor activation and was associated with an increase in cytoplasmic PtdIns(3,4,5)P3levels. In addition, leptin enhanced phosphorylation of the lipid phosphatase PTEN which inhibits PTEN function and elevates PtdIns(3,4,5)P3levels. Moreover, inhibition of PTEN mimicked and occluded the effects of leptin on GluR1 trafficking and excitatory synaptic strength. These data indicate that leptin, via a novel pathway involving PTEN inhibition, promotes GluR1 trafficking to hippocampal synapses. This process has important implications for the role of leptin in hippocampal synaptic function in health and disease. |
| Databáze: | OpenAIRE |
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