NMDA Receptor-Dependent Activation of the Small GTPase Rab5 Drives the Removal of Synaptic AMPA Receptors during Hippocampal LTD
The activity-dependent removal of AMPA receptors from synapses underlies long-term depression in hippocampal excitatory synapses. In this study, we have investigated the role of the small GTPase Rab5 during this process. We propose that Rab5 is a critical link between the signaling cascades triggere...
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| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 2005-01, Vol.45 (1), p.81-94 |
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| creator | Brown, Tyler C. Tran, Irwin C. Backos, Donald S. Esteban, José A. |
| description | The activity-dependent removal of AMPA receptors from synapses underlies long-term depression in hippocampal excitatory synapses. In this study, we have investigated the role of the small GTPase Rab5 during this process. We propose that Rab5 is a critical link between the signaling cascades triggered by LTD induction and the machinery that executes the activity-dependent removal of AMPA receptors. We have found that Rab5 activation drives the specific internalization of synaptic AMPA receptors in a clathrin-dependent manner and that this activity is required for LTD. Interestingly, Rab5 does not participate in the constitutive cycling of AMPA receptors. Rab5 is able to remove both GluR1 and GluR2 AMPA receptor subunits, leading to GluR1 dephosphorylation. Importantly, NMDA receptor-dependent LTD induction produces a rapid and transient increase of active (GTP bound) Rab5. We propose a model in which synaptic activity leads to Rab5 activation, which in turn drives the removal of AMPA receptors from synapses. |
| doi_str_mv | 10.1016/j.neuron.2004.12.023 |
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In this study, we have investigated the role of the small GTPase Rab5 during this process. We propose that Rab5 is a critical link between the signaling cascades triggered by LTD induction and the machinery that executes the activity-dependent removal of AMPA receptors. We have found that Rab5 activation drives the specific internalization of synaptic AMPA receptors in a clathrin-dependent manner and that this activity is required for LTD. Interestingly, Rab5 does not participate in the constitutive cycling of AMPA receptors. Rab5 is able to remove both GluR1 and GluR2 AMPA receptor subunits, leading to GluR1 dephosphorylation. Importantly, NMDA receptor-dependent LTD induction produces a rapid and transient increase of active (GTP bound) Rab5. We propose a model in which synaptic activity leads to Rab5 activation, which in turn drives the removal of AMPA receptors from synapses.</description><identifier>ISSN: 0896-6273</identifier><identifier>EISSN: 1097-4199</identifier><identifier>DOI: 10.1016/j.neuron.2004.12.023</identifier><identifier>PMID: 15629704</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Clathrin - metabolism ; Dendritic Spines - metabolism ; Dendritic Spines - ultrastructure ; Endocytosis - physiology ; Experiments ; Grants ; Hippocampus - metabolism ; Hippocampus - ultrastructure ; Humans ; Kinases ; Long-Term Synaptic Depression - physiology ; Microscopy ; Microscopy, Electron, Transmission ; Models, Neurological ; Neurons ; Organ Culture Techniques ; Patch-Clamp Techniques ; Phosphorylation ; Protein Transport - physiology ; Proteins ; rab5 GTP-Binding Proteins - metabolism ; Rats ; Receptors, AMPA - metabolism ; Receptors, N-Methyl-D-Aspartate - metabolism ; Synapses - metabolism ; Synapses - ultrastructure ; Synaptic Transmission - physiology ; Up-Regulation - physiology</subject><ispartof>Neuron (Cambridge, Mass.), 2005-01, Vol.45 (1), p.81-94</ispartof><rights>2005 Elsevier Inc.</rights><rights>Copyright Elsevier Limited Jan 6, 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-7b3eaf17a5212244588c49600d0318db1182bc6691e9b6be3cb024d485f6155d3</citedby><cites>FETCH-LOGICAL-c500t-7b3eaf17a5212244588c49600d0318db1182bc6691e9b6be3cb024d485f6155d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neuron.2004.12.023$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15629704$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brown, Tyler C.</creatorcontrib><creatorcontrib>Tran, Irwin C.</creatorcontrib><creatorcontrib>Backos, Donald S.</creatorcontrib><creatorcontrib>Esteban, José A.</creatorcontrib><title>NMDA Receptor-Dependent Activation of the Small GTPase Rab5 Drives the Removal of Synaptic AMPA Receptors during Hippocampal LTD</title><title>Neuron (Cambridge, Mass.)</title><addtitle>Neuron</addtitle><description>The activity-dependent removal of AMPA receptors from synapses underlies long-term depression in hippocampal excitatory synapses. In this study, we have investigated the role of the small GTPase Rab5 during this process. We propose that Rab5 is a critical link between the signaling cascades triggered by LTD induction and the machinery that executes the activity-dependent removal of AMPA receptors. We have found that Rab5 activation drives the specific internalization of synaptic AMPA receptors in a clathrin-dependent manner and that this activity is required for LTD. Interestingly, Rab5 does not participate in the constitutive cycling of AMPA receptors. Rab5 is able to remove both GluR1 and GluR2 AMPA receptor subunits, leading to GluR1 dephosphorylation. Importantly, NMDA receptor-dependent LTD induction produces a rapid and transient increase of active (GTP bound) Rab5. We propose a model in which synaptic activity leads to Rab5 activation, which in turn drives the removal of AMPA receptors from synapses.</description><subject>Animals</subject><subject>Clathrin - metabolism</subject><subject>Dendritic Spines - metabolism</subject><subject>Dendritic Spines - ultrastructure</subject><subject>Endocytosis - physiology</subject><subject>Experiments</subject><subject>Grants</subject><subject>Hippocampus - metabolism</subject><subject>Hippocampus - ultrastructure</subject><subject>Humans</subject><subject>Kinases</subject><subject>Long-Term Synaptic Depression - physiology</subject><subject>Microscopy</subject><subject>Microscopy, Electron, Transmission</subject><subject>Models, Neurological</subject><subject>Neurons</subject><subject>Organ Culture Techniques</subject><subject>Patch-Clamp Techniques</subject><subject>Phosphorylation</subject><subject>Protein Transport - physiology</subject><subject>Proteins</subject><subject>rab5 GTP-Binding Proteins - metabolism</subject><subject>Rats</subject><subject>Receptors, AMPA - metabolism</subject><subject>Receptors, N-Methyl-D-Aspartate - metabolism</subject><subject>Synapses - metabolism</subject><subject>Synapses - ultrastructure</subject><subject>Synaptic Transmission - physiology</subject><subject>Up-Regulation - physiology</subject><issn>0896-6273</issn><issn>1097-4199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcGO0zAQhi0EYsvCGyBkCYlbgsexnfiCVG1hF6kLq245W44zBVdJnLWTSnvj0UlppZU4cJrDfPPPaD5C3gLLgYH6uM97nGLoc86YyIHnjBfPyAKYLjMBWj8nC1ZplSleFhfkVUp7xkBIDS_JBUjFdcnEgvz-drta0g06HMYQsxUO2DfYj3TpRn-wow89DTs6_kJ639m2pdfbO5uQbmwt6Sr6A6a_zQ124WDbI3v_2Nth9I4ub--eohNtpuj7n_TGD0Nwthtmer1dvSYvdrZN-OZcL8mPL5-3VzfZ-vv116vlOnOSsTEr6wLtDkorOXAuhKwqJ7RirGEFVE0NUPHaKaUBda1qLFzNuGhEJXcKpGyKS_LhlDvE8DBhGk3nk8O2tT2GKRkoS16UqprB9_-A-zDFfr7NgGSFElqXaqbEiXIxpBRxZ4boOxsfDTBz9GP25uTHHP0Y4Gb2M4-9O4dPdYfN09BZyAx8OgE4_-LgMZrkPPYOGx_RjaYJ_v8b_gBQZKFh</recordid><startdate>20050106</startdate><enddate>20050106</enddate><creator>Brown, Tyler C.</creator><creator>Tran, Irwin C.</creator><creator>Backos, Donald S.</creator><creator>Esteban, José A.</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20050106</creationdate><title>NMDA Receptor-Dependent Activation of the Small GTPase Rab5 Drives the Removal of Synaptic AMPA Receptors during Hippocampal LTD</title><author>Brown, Tyler C. ; Tran, Irwin C. ; Backos, Donald S. ; Esteban, José A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c500t-7b3eaf17a5212244588c49600d0318db1182bc6691e9b6be3cb024d485f6155d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Clathrin - metabolism</topic><topic>Dendritic Spines - metabolism</topic><topic>Dendritic Spines - ultrastructure</topic><topic>Endocytosis - physiology</topic><topic>Experiments</topic><topic>Grants</topic><topic>Hippocampus - metabolism</topic><topic>Hippocampus - ultrastructure</topic><topic>Humans</topic><topic>Kinases</topic><topic>Long-Term Synaptic Depression - physiology</topic><topic>Microscopy</topic><topic>Microscopy, Electron, Transmission</topic><topic>Models, Neurological</topic><topic>Neurons</topic><topic>Organ Culture Techniques</topic><topic>Patch-Clamp Techniques</topic><topic>Phosphorylation</topic><topic>Protein Transport - physiology</topic><topic>Proteins</topic><topic>rab5 GTP-Binding Proteins - metabolism</topic><topic>Rats</topic><topic>Receptors, AMPA - metabolism</topic><topic>Receptors, N-Methyl-D-Aspartate - metabolism</topic><topic>Synapses - metabolism</topic><topic>Synapses - ultrastructure</topic><topic>Synaptic Transmission - physiology</topic><topic>Up-Regulation - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brown, Tyler C.</creatorcontrib><creatorcontrib>Tran, Irwin C.</creatorcontrib><creatorcontrib>Backos, Donald S.</creatorcontrib><creatorcontrib>Esteban, José A.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Neuron (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brown, Tyler C.</au><au>Tran, Irwin C.</au><au>Backos, Donald S.</au><au>Esteban, José A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NMDA Receptor-Dependent Activation of the Small GTPase Rab5 Drives the Removal of Synaptic AMPA Receptors during Hippocampal LTD</atitle><jtitle>Neuron (Cambridge, Mass.)</jtitle><addtitle>Neuron</addtitle><date>2005-01-06</date><risdate>2005</risdate><volume>45</volume><issue>1</issue><spage>81</spage><epage>94</epage><pages>81-94</pages><issn>0896-6273</issn><eissn>1097-4199</eissn><abstract>The activity-dependent removal of AMPA receptors from synapses underlies long-term depression in hippocampal excitatory synapses. In this study, we have investigated the role of the small GTPase Rab5 during this process. We propose that Rab5 is a critical link between the signaling cascades triggered by LTD induction and the machinery that executes the activity-dependent removal of AMPA receptors. We have found that Rab5 activation drives the specific internalization of synaptic AMPA receptors in a clathrin-dependent manner and that this activity is required for LTD. Interestingly, Rab5 does not participate in the constitutive cycling of AMPA receptors. Rab5 is able to remove both GluR1 and GluR2 AMPA receptor subunits, leading to GluR1 dephosphorylation. Importantly, NMDA receptor-dependent LTD induction produces a rapid and transient increase of active (GTP bound) Rab5. 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| source | MEDLINE; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Access via ScienceDirect (Elsevier) |
| subjects | Animals Clathrin - metabolism Dendritic Spines - metabolism Dendritic Spines - ultrastructure Endocytosis - physiology Experiments Grants Hippocampus - metabolism Hippocampus - ultrastructure Humans Kinases Long-Term Synaptic Depression - physiology Microscopy Microscopy, Electron, Transmission Models, Neurological Neurons Organ Culture Techniques Patch-Clamp Techniques Phosphorylation Protein Transport - physiology Proteins rab5 GTP-Binding Proteins - metabolism Rats Receptors, AMPA - metabolism Receptors, N-Methyl-D-Aspartate - metabolism Synapses - metabolism Synapses - ultrastructure Synaptic Transmission - physiology Up-Regulation - physiology |
| title | NMDA Receptor-Dependent Activation of the Small GTPase Rab5 Drives the Removal of Synaptic AMPA Receptors during Hippocampal LTD |
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