Human Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) Regulates Dendritic Morphogenesis
Disturbances of synaptic connectivity during perinatal and adolescent periods have been hypothesized to be related to the pathophysiology of schizophrenia. Rho guanine nucleotide exchange factor 11 (ARHGEF11) is a specific guanine nucleotide exchange factors (GEF) for RhoA, which is a critical regul...
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| Veröffentlicht in: | International journal of molecular sciences 2016-12, Vol.18 (1), p.67-67 |
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| creator | Mizuki, Yutaka Takaki, Manabu Sakamoto, Shinji Okamoto, Sojiro Kishimoto, Makiko Okahisa, Yuko Itoh, Masahiko Yamada, Norihito |
| description | Disturbances of synaptic connectivity during perinatal and adolescent periods have been hypothesized to be related to the pathophysiology of schizophrenia. Rho guanine nucleotide exchange factor 11 (ARHGEF11) is a specific guanine nucleotide exchange factors (GEF) for RhoA, which is a critical regulator of actin cytoskeleton dynamics and organization of dendritic spines and inhibitor of spine maintenance.
variants are reported to be associated with a higher risk for the onset of schizophrenia in a Japanese population; however, how ARHGEF11 contributes to the pathogenesis of schizophrenia in dendritic spines is unknown. Therefore, we first studied the distribution, binding, and function of ARHGEF11 in the dendritic spines of the rat cerebral cortex. After subcellular fractionation of the rat cerebral cortex, ARHGEF11 was detected with synaptophysin and post-synaptic density protein 95 (PSD-95) in the P2 fractions including synaptosomal fractions containing presynaptic and postsynaptic density proteins. Endogenous ARHGEF11 was coimmunoprecipitated with synaptophysin or PSD-95. In cortical primary neurons at 28 days in vitro, immunostaining revealed that ARHGEF11 located in the dendrites and dendritic spines and colocalized with PSD-95 and synaptophysin. Overexpression of exogenous ARHGEF11 significantly decreased the number of spines (
= 0.008). These results indicate that ARHGEF11 is likely to be associated with synaptic membranes and regulation of spine. |
| doi_str_mv | 10.3390/ijms18010067 |
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variants are reported to be associated with a higher risk for the onset of schizophrenia in a Japanese population; however, how ARHGEF11 contributes to the pathogenesis of schizophrenia in dendritic spines is unknown. Therefore, we first studied the distribution, binding, and function of ARHGEF11 in the dendritic spines of the rat cerebral cortex. After subcellular fractionation of the rat cerebral cortex, ARHGEF11 was detected with synaptophysin and post-synaptic density protein 95 (PSD-95) in the P2 fractions including synaptosomal fractions containing presynaptic and postsynaptic density proteins. Endogenous ARHGEF11 was coimmunoprecipitated with synaptophysin or PSD-95. In cortical primary neurons at 28 days in vitro, immunostaining revealed that ARHGEF11 located in the dendrites and dendritic spines and colocalized with PSD-95 and synaptophysin. Overexpression of exogenous ARHGEF11 significantly decreased the number of spines (
= 0.008). These results indicate that ARHGEF11 is likely to be associated with synaptic membranes and regulation of spine.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms18010067</identifier><identifier>PMID: 28036092</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Actin ; Animals ; Cells, Cultured ; Cerebral cortex ; Cerebral Cortex - cytology ; Cytoskeleton ; Dendritic spines ; Dendritic Spines - metabolism ; Disks Large Homolog 4 Protein ; Fractionation ; Guanine ; Guanine nucleotide exchange factor ; Humans ; In vitro methods and tests ; Intracellular Signaling Peptides and Proteins - metabolism ; Membrane Proteins - metabolism ; Membranes ; Mental disorders ; Morphogenesis ; Neural networks ; Neurogenesis ; Postsynaptic density ; Postsynaptic density proteins ; Protein Transport ; Proteins ; Rats ; Rats, Sprague-Dawley ; Rho Guanine Nucleotide Exchange Factors - genetics ; Rho Guanine Nucleotide Exchange Factors - metabolism ; RhoA protein ; Rodents ; Schizophrenia ; Spine ; Synaptic density ; Synaptic membranes ; Synaptophysin ; Synaptophysin - metabolism</subject><ispartof>International journal of molecular sciences, 2016-12, Vol.18 (1), p.67-67</ispartof><rights>Copyright MDPI AG 2017</rights><rights>2016 by the authors; licensee MDPI, Basel, Switzerland. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c511t-723ba2f8deb019e7afc8a18a888440ec5c5fb0f40bc61de76df15ba65f3849803</citedby><cites>FETCH-LOGICAL-c511t-723ba2f8deb019e7afc8a18a888440ec5c5fb0f40bc61de76df15ba65f3849803</cites><orcidid>0000-0002-5534-3778</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297702/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297702/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28036092$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mizuki, Yutaka</creatorcontrib><creatorcontrib>Takaki, Manabu</creatorcontrib><creatorcontrib>Sakamoto, Shinji</creatorcontrib><creatorcontrib>Okamoto, Sojiro</creatorcontrib><creatorcontrib>Kishimoto, Makiko</creatorcontrib><creatorcontrib>Okahisa, Yuko</creatorcontrib><creatorcontrib>Itoh, Masahiko</creatorcontrib><creatorcontrib>Yamada, Norihito</creatorcontrib><title>Human Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) Regulates Dendritic Morphogenesis</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Disturbances of synaptic connectivity during perinatal and adolescent periods have been hypothesized to be related to the pathophysiology of schizophrenia. Rho guanine nucleotide exchange factor 11 (ARHGEF11) is a specific guanine nucleotide exchange factors (GEF) for RhoA, which is a critical regulator of actin cytoskeleton dynamics and organization of dendritic spines and inhibitor of spine maintenance.
variants are reported to be associated with a higher risk for the onset of schizophrenia in a Japanese population; however, how ARHGEF11 contributes to the pathogenesis of schizophrenia in dendritic spines is unknown. Therefore, we first studied the distribution, binding, and function of ARHGEF11 in the dendritic spines of the rat cerebral cortex. After subcellular fractionation of the rat cerebral cortex, ARHGEF11 was detected with synaptophysin and post-synaptic density protein 95 (PSD-95) in the P2 fractions including synaptosomal fractions containing presynaptic and postsynaptic density proteins. Endogenous ARHGEF11 was coimmunoprecipitated with synaptophysin or PSD-95. In cortical primary neurons at 28 days in vitro, immunostaining revealed that ARHGEF11 located in the dendrites and dendritic spines and colocalized with PSD-95 and synaptophysin. Overexpression of exogenous ARHGEF11 significantly decreased the number of spines (
= 0.008). These results indicate that ARHGEF11 is likely to be associated with synaptic membranes and regulation of spine.</description><subject>Actin</subject><subject>Animals</subject><subject>Cells, Cultured</subject><subject>Cerebral cortex</subject><subject>Cerebral Cortex - cytology</subject><subject>Cytoskeleton</subject><subject>Dendritic spines</subject><subject>Dendritic Spines - metabolism</subject><subject>Disks Large Homolog 4 Protein</subject><subject>Fractionation</subject><subject>Guanine</subject><subject>Guanine nucleotide exchange factor</subject><subject>Humans</subject><subject>In vitro methods and tests</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Membrane Proteins - metabolism</subject><subject>Membranes</subject><subject>Mental disorders</subject><subject>Morphogenesis</subject><subject>Neural networks</subject><subject>Neurogenesis</subject><subject>Postsynaptic density</subject><subject>Postsynaptic density proteins</subject><subject>Protein Transport</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rho Guanine Nucleotide Exchange Factors - genetics</subject><subject>Rho Guanine Nucleotide Exchange Factors - metabolism</subject><subject>RhoA protein</subject><subject>Rodents</subject><subject>Schizophrenia</subject><subject>Spine</subject><subject>Synaptic density</subject><subject>Synaptic membranes</subject><subject>Synaptophysin</subject><subject>Synaptophysin - metabolism</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkUtr3DAURkVJSNJJdl0XQTYJdFpdyQ95UwjJPAJpA0OyKwhZvp7RYEtTyS7tv69NHky7ykoXdDjc-32EfAD2WYiCfbHbNoJkwFiWvyMnkHA-HeeDvfmYvI9xyxgXPC2OyDGXTGSs4Cfkx7JvtaOrjaeLXjvrkH7vTYO-sxXS2W-z0W6NdK5N5wMFoBdXq-ViNge4pCtc943uMNIbdFWwnTX0mw-7jV-jw2jjKTmsdRPx7PmdkMf57OF6Ob27X9xeX91NTQrQTXMuSs1rWWHJoMBc10ZqkFpKmSQMTWrSumR1wkqTQYV5VtWQljpLayGTYjhlQr4-eXd92WJl0HVBN2oXbKvDH-W1Vf_-OLtRa_9LpbzI8yGVCbl4FgT_s8fYqdZGg02jHfo-KpCZFDwRsngDmibZEHw2Ws__Q7e-D25IYhRyAFEko_DTE2WCjzFg_bo3MDU2rPYbHvCP-7e-wi-Vir-mY6B2</recordid><startdate>20161229</startdate><enddate>20161229</enddate><creator>Mizuki, Yutaka</creator><creator>Takaki, Manabu</creator><creator>Sakamoto, Shinji</creator><creator>Okamoto, Sojiro</creator><creator>Kishimoto, Makiko</creator><creator>Okahisa, Yuko</creator><creator>Itoh, Masahiko</creator><creator>Yamada, Norihito</creator><general>MDPI AG</general><general>MDPI</general><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>7TK</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5534-3778</orcidid></search><sort><creationdate>20161229</creationdate><title>Human Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) Regulates Dendritic Morphogenesis</title><author>Mizuki, Yutaka ; Takaki, Manabu ; Sakamoto, Shinji ; Okamoto, Sojiro ; Kishimoto, Makiko ; Okahisa, Yuko ; Itoh, Masahiko ; Yamada, Norihito</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c511t-723ba2f8deb019e7afc8a18a888440ec5c5fb0f40bc61de76df15ba65f3849803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Actin</topic><topic>Animals</topic><topic>Cells, Cultured</topic><topic>Cerebral cortex</topic><topic>Cerebral Cortex - cytology</topic><topic>Cytoskeleton</topic><topic>Dendritic spines</topic><topic>Dendritic Spines - metabolism</topic><topic>Disks Large Homolog 4 Protein</topic><topic>Fractionation</topic><topic>Guanine</topic><topic>Guanine nucleotide exchange factor</topic><topic>Humans</topic><topic>In vitro methods and tests</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Membrane Proteins - metabolism</topic><topic>Membranes</topic><topic>Mental disorders</topic><topic>Morphogenesis</topic><topic>Neural networks</topic><topic>Neurogenesis</topic><topic>Postsynaptic density</topic><topic>Postsynaptic density proteins</topic><topic>Protein Transport</topic><topic>Proteins</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rho Guanine Nucleotide Exchange Factors - genetics</topic><topic>Rho Guanine Nucleotide Exchange Factors - metabolism</topic><topic>RhoA protein</topic><topic>Rodents</topic><topic>Schizophrenia</topic><topic>Spine</topic><topic>Synaptic density</topic><topic>Synaptic membranes</topic><topic>Synaptophysin</topic><topic>Synaptophysin - 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Academic</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mizuki, Yutaka</au><au>Takaki, Manabu</au><au>Sakamoto, Shinji</au><au>Okamoto, Sojiro</au><au>Kishimoto, Makiko</au><au>Okahisa, Yuko</au><au>Itoh, Masahiko</au><au>Yamada, Norihito</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) Regulates Dendritic Morphogenesis</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2016-12-29</date><risdate>2016</risdate><volume>18</volume><issue>1</issue><spage>67</spage><epage>67</epage><pages>67-67</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Disturbances of synaptic connectivity during perinatal and adolescent periods have been hypothesized to be related to the pathophysiology of schizophrenia. Rho guanine nucleotide exchange factor 11 (ARHGEF11) is a specific guanine nucleotide exchange factors (GEF) for RhoA, which is a critical regulator of actin cytoskeleton dynamics and organization of dendritic spines and inhibitor of spine maintenance.
variants are reported to be associated with a higher risk for the onset of schizophrenia in a Japanese population; however, how ARHGEF11 contributes to the pathogenesis of schizophrenia in dendritic spines is unknown. Therefore, we first studied the distribution, binding, and function of ARHGEF11 in the dendritic spines of the rat cerebral cortex. After subcellular fractionation of the rat cerebral cortex, ARHGEF11 was detected with synaptophysin and post-synaptic density protein 95 (PSD-95) in the P2 fractions including synaptosomal fractions containing presynaptic and postsynaptic density proteins. Endogenous ARHGEF11 was coimmunoprecipitated with synaptophysin or PSD-95. In cortical primary neurons at 28 days in vitro, immunostaining revealed that ARHGEF11 located in the dendrites and dendritic spines and colocalized with PSD-95 and synaptophysin. Overexpression of exogenous ARHGEF11 significantly decreased the number of spines (
= 0.008). These results indicate that ARHGEF11 is likely to be associated with synaptic membranes and regulation of spine.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>28036092</pmid><doi>10.3390/ijms18010067</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-5534-3778</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Actin Animals Cells, Cultured Cerebral cortex Cerebral Cortex - cytology Cytoskeleton Dendritic spines Dendritic Spines - metabolism Disks Large Homolog 4 Protein Fractionation Guanine Guanine nucleotide exchange factor Humans In vitro methods and tests Intracellular Signaling Peptides and Proteins - metabolism Membrane Proteins - metabolism Membranes Mental disorders Morphogenesis Neural networks Neurogenesis Postsynaptic density Postsynaptic density proteins Protein Transport Proteins Rats Rats, Sprague-Dawley Rho Guanine Nucleotide Exchange Factors - genetics Rho Guanine Nucleotide Exchange Factors - metabolism RhoA protein Rodents Schizophrenia Spine Synaptic density Synaptic membranes Synaptophysin Synaptophysin - metabolism |
| title | Human Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) Regulates Dendritic Morphogenesis |
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