Galectin-3 Negatively Regulates Hippocampus-Dependent Memory Formation through Inhibition of Integrin Signaling and Galectin-3 Phosphorylation
Galectin-3, a member of the galectin protein family, has been found to regulate cell proliferation, inhibit apoptosis and promote inflammatory responses. Galectin-3 is also expressed in the adult rat hippocampus, but its role in learning and memory function is not known. Here, we found that contextu...
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| Format: | Article |
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Frontiers Media S.A.
2017-07-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00217/full |
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| author | Yan-Chu Chen Yun-Li Ma Cheng-Hsiung Lin Sin-Jhong Cheng Sin-Jhong Cheng Wei-Lun Hsu Eminy H.-Y. Lee Eminy H.-Y. Lee |
| author_facet | Yan-Chu Chen Yun-Li Ma Cheng-Hsiung Lin Sin-Jhong Cheng Sin-Jhong Cheng Wei-Lun Hsu Eminy H.-Y. Lee Eminy H.-Y. Lee |
| author_sort | Yan-Chu Chen |
| collection | DOAJ |
| description | Galectin-3, a member of the galectin protein family, has been found to regulate cell proliferation, inhibit apoptosis and promote inflammatory responses. Galectin-3 is also expressed in the adult rat hippocampus, but its role in learning and memory function is not known. Here, we found that contextual fear-conditioning training, spatial training or injection of NMDA into the rat CA1 area each dramatically decreased the level of endogenous galectin-3 expression. Overexpression of galectin-3 impaired fear memory, whereas galectin-3 knockout (KO) enhanced fear retention, spatial memory and hippocampal long-term potentiation. Galectin-3 was further found to associate with integrin α3, an association that was decreased after fear-conditioning training. Transfection of the rat CA1 area with small interfering RNA against galectin-3 facilitated fear memory and increased phosphorylated focal adhesion kinase (FAK) levels, effects that were blocked by co-transfection of the FAK phosphorylation-defective mutant Flag-FAKY397F. Notably, levels of serine-phosphorylated galectin-3 were decreased by fear conditioning training. In addition, blockade of galectin-3 phosphorylation at Ser-6 facilitated fear memory, whereas constitutive activation of galectin-3 at Ser-6 impaired fear memory. Interestingly galectin-1 plays a role in fear-memory formation similar to that of galectin-3. Collectively, our data provide the first demonstration that galectin-3 is a novel negative regulator of memory formation that exerts its effects through both extracellular and intracellular mechanisms. |
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| id | doaj.art-2b23373bc0924e8d82b818e52f3e74a8 |
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| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-13T07:50:06Z |
| publishDate | 2017-07-01 |
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| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-2b23373bc0924e8d82b818e52f3e74a82022-12-22T02:55:33ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992017-07-011010.3389/fnmol.2017.00217266160Galectin-3 Negatively Regulates Hippocampus-Dependent Memory Formation through Inhibition of Integrin Signaling and Galectin-3 PhosphorylationYan-Chu Chen0Yun-Li Ma1Cheng-Hsiung Lin2Sin-Jhong Cheng3Sin-Jhong Cheng4Wei-Lun Hsu5Eminy H.-Y. Lee6Eminy H.-Y. Lee7Graduate Institute of Life Sciences, National Defense Medical CenterTaipei, TaiwanInstitute of Biomedical Sciences, Academia SinicaTaipei, TaiwanInstitute of Biomedical Sciences, Academia SinicaTaipei, TaiwanInstitute of Biomedical Sciences, Academia SinicaTaipei, TaiwanNeuroscience Program in Academia SinicaTaipei, TaiwanInstitute of Biomedical Sciences, Academia SinicaTaipei, TaiwanGraduate Institute of Life Sciences, National Defense Medical CenterTaipei, TaiwanInstitute of Biomedical Sciences, Academia SinicaTaipei, TaiwanGalectin-3, a member of the galectin protein family, has been found to regulate cell proliferation, inhibit apoptosis and promote inflammatory responses. Galectin-3 is also expressed in the adult rat hippocampus, but its role in learning and memory function is not known. Here, we found that contextual fear-conditioning training, spatial training or injection of NMDA into the rat CA1 area each dramatically decreased the level of endogenous galectin-3 expression. Overexpression of galectin-3 impaired fear memory, whereas galectin-3 knockout (KO) enhanced fear retention, spatial memory and hippocampal long-term potentiation. Galectin-3 was further found to associate with integrin α3, an association that was decreased after fear-conditioning training. Transfection of the rat CA1 area with small interfering RNA against galectin-3 facilitated fear memory and increased phosphorylated focal adhesion kinase (FAK) levels, effects that were blocked by co-transfection of the FAK phosphorylation-defective mutant Flag-FAKY397F. Notably, levels of serine-phosphorylated galectin-3 were decreased by fear conditioning training. In addition, blockade of galectin-3 phosphorylation at Ser-6 facilitated fear memory, whereas constitutive activation of galectin-3 at Ser-6 impaired fear memory. Interestingly galectin-1 plays a role in fear-memory formation similar to that of galectin-3. Collectively, our data provide the first demonstration that galectin-3 is a novel negative regulator of memory formation that exerts its effects through both extracellular and intracellular mechanisms.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00217/fullgalectin-3integrin signalingphosphorylationcontextual fear conditioning learningspatial learninghippocampus |
| spellingShingle | Yan-Chu Chen Yun-Li Ma Cheng-Hsiung Lin Sin-Jhong Cheng Sin-Jhong Cheng Wei-Lun Hsu Eminy H.-Y. Lee Eminy H.-Y. Lee Galectin-3 Negatively Regulates Hippocampus-Dependent Memory Formation through Inhibition of Integrin Signaling and Galectin-3 Phosphorylation Frontiers in Molecular Neuroscience galectin-3 integrin signaling phosphorylation contextual fear conditioning learning spatial learning hippocampus |
| title | Galectin-3 Negatively Regulates Hippocampus-Dependent Memory Formation through Inhibition of Integrin Signaling and Galectin-3 Phosphorylation |
| title_full | Galectin-3 Negatively Regulates Hippocampus-Dependent Memory Formation through Inhibition of Integrin Signaling and Galectin-3 Phosphorylation |
| title_fullStr | Galectin-3 Negatively Regulates Hippocampus-Dependent Memory Formation through Inhibition of Integrin Signaling and Galectin-3 Phosphorylation |
| title_full_unstemmed | Galectin-3 Negatively Regulates Hippocampus-Dependent Memory Formation through Inhibition of Integrin Signaling and Galectin-3 Phosphorylation |
| title_short | Galectin-3 Negatively Regulates Hippocampus-Dependent Memory Formation through Inhibition of Integrin Signaling and Galectin-3 Phosphorylation |
| title_sort | galectin 3 negatively regulates hippocampus dependent memory formation through inhibition of integrin signaling and galectin 3 phosphorylation |
| topic | galectin-3 integrin signaling phosphorylation contextual fear conditioning learning spatial learning hippocampus |
| url | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00217/full |
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