A neuropeptide signaling pathway regulates synaptic growth in Drosophila
Neuropeptide signaling is integral to many aspects of neural communication, particularly modulation of membrane excitability and synaptic transmission. However, neuropeptides have not been clearly implicated in synaptic growth and development. Here, we demonstrate that cholecystokinin-like receptor...
Gespeichert in:
| Veröffentlicht in: | The Journal of cell biology 2012-02, Vol.196 (4), p.529-543 |
|---|---|
| Hauptverfasser: | , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 543 |
|---|---|
| container_issue | 4 |
| container_start_page | 529 |
| container_title | The Journal of cell biology |
| container_volume | 196 |
| creator | Chen, Xu Ganetzky, Barry |
| description | Neuropeptide signaling is integral to many aspects of neural communication, particularly modulation of membrane excitability and synaptic transmission. However, neuropeptides have not been clearly implicated in synaptic growth and development. Here, we demonstrate that cholecystokinin-like receptor (CCKLR) and drosulfakinin (DSK), its predicted ligand, are strong positive growth regulators of the Drosophila melanogaster larval neuromuscular junction (NMJ). Mutations of CCKLR or dsk produced severe NMJ undergrowth, whereas overexpression of CCKLR caused overgrowth. Presynaptic expression of CCKLR was necessary and sufficient for regulating NMJ growth. CCKLR and dsk mutants also reduced synaptic function in parallel with decreased NMJ size. Analysis of double mutants revealed that DSK/CCKLR regulation of NMJ growth occurs through the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element binding protein (CREB) pathway. Our results demonstrate a novel role for neuropeptide signaling in synaptic development. Moreover, because the cAMP-PKA-CREB pathway is required for structural synaptic plasticity in learning and memory, DSK/CCKLR signaling may also contribute to these mechanisms. |
| doi_str_mv | 10.1083/jcb.201109044 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3283997</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2602840381</sourcerecordid><originalsourceid>FETCH-LOGICAL-c512t-a1c2bfaf767f153138e9170c88c976c540eb1fefad989571ba4aff6b0014bc2a3</originalsourceid><addsrcrecordid>eNp9kTFv1DAYhi0EoteDkRVFLHRJ-322E9sLUtUWilSpC8yW47NzPuXiYCdU9-9x1XICBiYP36NHr9-XkHcI5wiSXexsd04BERRw_oKssOFQS-TwkqwAKNaqoc0JOc15BwBccPaanFDKGErerMjtZTW6JcXJTXPYuCqHfjRDGPtqMvP2wRyq5PplMLPLVT6MplC26lN8mLdVGKvrFHOctmEwb8grb4bs3j6_a_L98823q9v67v7L16vLu9o2SOfaoKWdN160wmPDkEmnUICV0irR2hLedeidNxslVSOwM9x433YAyDtLDVuTT0_eaen2bmPdOCcz6CmFvUkHHU3Qf1_GsNV9_KkZlUwpUQQfnwUp_lhcnvU-ZOuGwYwuLlkrSkXLoIRbk7P_ksgokxQ4VQX98A-6i0sqTT76Wo5MlMrXpH6CbGktJ-ePqRH045i6jKmPYxb-_Z9fPdK_12O_AF7Dm2s</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>926413722</pqid></control><display><type>article</type><title>A neuropeptide signaling pathway regulates synaptic growth in Drosophila</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Chen, Xu ; Ganetzky, Barry</creator><creatorcontrib>Chen, Xu ; Ganetzky, Barry</creatorcontrib><description>Neuropeptide signaling is integral to many aspects of neural communication, particularly modulation of membrane excitability and synaptic transmission. However, neuropeptides have not been clearly implicated in synaptic growth and development. Here, we demonstrate that cholecystokinin-like receptor (CCKLR) and drosulfakinin (DSK), its predicted ligand, are strong positive growth regulators of the Drosophila melanogaster larval neuromuscular junction (NMJ). Mutations of CCKLR or dsk produced severe NMJ undergrowth, whereas overexpression of CCKLR caused overgrowth. Presynaptic expression of CCKLR was necessary and sufficient for regulating NMJ growth. CCKLR and dsk mutants also reduced synaptic function in parallel with decreased NMJ size. Analysis of double mutants revealed that DSK/CCKLR regulation of NMJ growth occurs through the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element binding protein (CREB) pathway. Our results demonstrate a novel role for neuropeptide signaling in synaptic development. Moreover, because the cAMP-PKA-CREB pathway is required for structural synaptic plasticity in learning and memory, DSK/CCKLR signaling may also contribute to these mechanisms.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.201109044</identifier><identifier>PMID: 22331845</identifier><identifier>CODEN: JCLBA3</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Animals ; Animals, Genetically Modified ; Binding sites ; Cellular biology ; Cloning, Molecular ; Cyclic AMP - metabolism ; Cyclic AMP Response Element-Binding Protein - genetics ; Cyclic AMP Response Element-Binding Protein - metabolism ; Cyclic AMP-Dependent Protein Kinases - genetics ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Drosophila melanogaster ; Drosophila melanogaster - genetics ; Drosophila melanogaster - metabolism ; Drosophila Proteins - genetics ; Drosophila Proteins - metabolism ; Electrophysiology ; Female ; Immunoenzyme Techniques ; Insects ; Kinases ; Larva - growth & development ; Larva - metabolism ; Male ; Mutation ; Mutation - genetics ; Neuromuscular Junction - physiology ; Neuropeptides - genetics ; Neuropeptides - metabolism ; Oligopeptides - genetics ; Oligopeptides - metabolism ; Presynaptic Terminals - metabolism ; Proteins ; Receptors, Cholecystokinin - genetics ; Receptors, Cholecystokinin - metabolism ; Signal Transduction ; Synapses - metabolism ; Synaptic Transmission - physiology</subject><ispartof>The Journal of cell biology, 2012-02, Vol.196 (4), p.529-543</ispartof><rights>Copyright Rockefeller University Press Feb 20, 2012</rights><rights>2012 Chen and Ganetzky 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c512t-a1c2bfaf767f153138e9170c88c976c540eb1fefad989571ba4aff6b0014bc2a3</citedby><cites>FETCH-LOGICAL-c512t-a1c2bfaf767f153138e9170c88c976c540eb1fefad989571ba4aff6b0014bc2a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22331845$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Xu</creatorcontrib><creatorcontrib>Ganetzky, Barry</creatorcontrib><title>A neuropeptide signaling pathway regulates synaptic growth in Drosophila</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>Neuropeptide signaling is integral to many aspects of neural communication, particularly modulation of membrane excitability and synaptic transmission. However, neuropeptides have not been clearly implicated in synaptic growth and development. Here, we demonstrate that cholecystokinin-like receptor (CCKLR) and drosulfakinin (DSK), its predicted ligand, are strong positive growth regulators of the Drosophila melanogaster larval neuromuscular junction (NMJ). Mutations of CCKLR or dsk produced severe NMJ undergrowth, whereas overexpression of CCKLR caused overgrowth. Presynaptic expression of CCKLR was necessary and sufficient for regulating NMJ growth. CCKLR and dsk mutants also reduced synaptic function in parallel with decreased NMJ size. Analysis of double mutants revealed that DSK/CCKLR regulation of NMJ growth occurs through the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element binding protein (CREB) pathway. Our results demonstrate a novel role for neuropeptide signaling in synaptic development. Moreover, because the cAMP-PKA-CREB pathway is required for structural synaptic plasticity in learning and memory, DSK/CCKLR signaling may also contribute to these mechanisms.</description><subject>Animals</subject><subject>Animals, Genetically Modified</subject><subject>Binding sites</subject><subject>Cellular biology</subject><subject>Cloning, Molecular</subject><subject>Cyclic AMP - metabolism</subject><subject>Cyclic AMP Response Element-Binding Protein - genetics</subject><subject>Cyclic AMP Response Element-Binding Protein - metabolism</subject><subject>Cyclic AMP-Dependent Protein Kinases - genetics</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Drosophila melanogaster</subject><subject>Drosophila melanogaster - genetics</subject><subject>Drosophila melanogaster - metabolism</subject><subject>Drosophila Proteins - genetics</subject><subject>Drosophila Proteins - metabolism</subject><subject>Electrophysiology</subject><subject>Female</subject><subject>Immunoenzyme Techniques</subject><subject>Insects</subject><subject>Kinases</subject><subject>Larva - growth & development</subject><subject>Larva - metabolism</subject><subject>Male</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>Neuromuscular Junction - physiology</subject><subject>Neuropeptides - genetics</subject><subject>Neuropeptides - metabolism</subject><subject>Oligopeptides - genetics</subject><subject>Oligopeptides - metabolism</subject><subject>Presynaptic Terminals - metabolism</subject><subject>Proteins</subject><subject>Receptors, Cholecystokinin - genetics</subject><subject>Receptors, Cholecystokinin - metabolism</subject><subject>Signal Transduction</subject><subject>Synapses - metabolism</subject><subject>Synaptic Transmission - physiology</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kTFv1DAYhi0EoteDkRVFLHRJ-322E9sLUtUWilSpC8yW47NzPuXiYCdU9-9x1XICBiYP36NHr9-XkHcI5wiSXexsd04BERRw_oKssOFQS-TwkqwAKNaqoc0JOc15BwBccPaanFDKGErerMjtZTW6JcXJTXPYuCqHfjRDGPtqMvP2wRyq5PplMLPLVT6MplC26lN8mLdVGKvrFHOctmEwb8grb4bs3j6_a_L98823q9v67v7L16vLu9o2SOfaoKWdN160wmPDkEmnUICV0irR2hLedeidNxslVSOwM9x433YAyDtLDVuTT0_eaen2bmPdOCcz6CmFvUkHHU3Qf1_GsNV9_KkZlUwpUQQfnwUp_lhcnvU-ZOuGwYwuLlkrSkXLoIRbk7P_ksgokxQ4VQX98A-6i0sqTT76Wo5MlMrXpH6CbGktJ-ePqRH045i6jKmPYxb-_Z9fPdK_12O_AF7Dm2s</recordid><startdate>20120220</startdate><enddate>20120220</enddate><creator>Chen, Xu</creator><creator>Ganetzky, Barry</creator><general>Rockefeller University Press</general><general>The Rockefeller University Press</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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20120220</creationdate><title>A neuropeptide signaling pathway regulates synaptic growth in Drosophila</title><author>Chen, Xu ; Ganetzky, Barry</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c512t-a1c2bfaf767f153138e9170c88c976c540eb1fefad989571ba4aff6b0014bc2a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Animals, Genetically Modified</topic><topic>Binding sites</topic><topic>Cellular biology</topic><topic>Cloning, Molecular</topic><topic>Cyclic AMP - metabolism</topic><topic>Cyclic AMP Response Element-Binding Protein - genetics</topic><topic>Cyclic AMP Response Element-Binding Protein - metabolism</topic><topic>Cyclic AMP-Dependent Protein Kinases - genetics</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>Drosophila melanogaster</topic><topic>Drosophila melanogaster - genetics</topic><topic>Drosophila melanogaster - metabolism</topic><topic>Drosophila Proteins - genetics</topic><topic>Drosophila Proteins - metabolism</topic><topic>Electrophysiology</topic><topic>Female</topic><topic>Immunoenzyme Techniques</topic><topic>Insects</topic><topic>Kinases</topic><topic>Larva - growth & development</topic><topic>Larva - metabolism</topic><topic>Male</topic><topic>Mutation</topic><topic>Mutation - genetics</topic><topic>Neuromuscular Junction - physiology</topic><topic>Neuropeptides - genetics</topic><topic>Neuropeptides - metabolism</topic><topic>Oligopeptides - genetics</topic><topic>Oligopeptides - metabolism</topic><topic>Presynaptic Terminals - metabolism</topic><topic>Proteins</topic><topic>Receptors, Cholecystokinin - genetics</topic><topic>Receptors, Cholecystokinin - metabolism</topic><topic>Signal Transduction</topic><topic>Synapses - metabolism</topic><topic>Synaptic Transmission - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Xu</creatorcontrib><creatorcontrib>Ganetzky, Barry</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Xu</au><au>Ganetzky, Barry</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A neuropeptide signaling pathway regulates synaptic growth in Drosophila</atitle><jtitle>The Journal of cell biology</jtitle><addtitle>J Cell Biol</addtitle><date>2012-02-20</date><risdate>2012</risdate><volume>196</volume><issue>4</issue><spage>529</spage><epage>543</epage><pages>529-543</pages><issn>0021-9525</issn><eissn>1540-8140</eissn><coden>JCLBA3</coden><abstract>Neuropeptide signaling is integral to many aspects of neural communication, particularly modulation of membrane excitability and synaptic transmission. However, neuropeptides have not been clearly implicated in synaptic growth and development. Here, we demonstrate that cholecystokinin-like receptor (CCKLR) and drosulfakinin (DSK), its predicted ligand, are strong positive growth regulators of the Drosophila melanogaster larval neuromuscular junction (NMJ). Mutations of CCKLR or dsk produced severe NMJ undergrowth, whereas overexpression of CCKLR caused overgrowth. Presynaptic expression of CCKLR was necessary and sufficient for regulating NMJ growth. CCKLR and dsk mutants also reduced synaptic function in parallel with decreased NMJ size. Analysis of double mutants revealed that DSK/CCKLR regulation of NMJ growth occurs through the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element binding protein (CREB) pathway. Our results demonstrate a novel role for neuropeptide signaling in synaptic development. Moreover, because the cAMP-PKA-CREB pathway is required for structural synaptic plasticity in learning and memory, DSK/CCKLR signaling may also contribute to these mechanisms.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>22331845</pmid><doi>10.1083/jcb.201109044</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9525 |
| ispartof | The Journal of cell biology, 2012-02, Vol.196 (4), p.529-543 |
| issn | 0021-9525 1540-8140 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3283997 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Animals, Genetically Modified Binding sites Cellular biology Cloning, Molecular Cyclic AMP - metabolism Cyclic AMP Response Element-Binding Protein - genetics Cyclic AMP Response Element-Binding Protein - metabolism Cyclic AMP-Dependent Protein Kinases - genetics Cyclic AMP-Dependent Protein Kinases - metabolism Drosophila melanogaster Drosophila melanogaster - genetics Drosophila melanogaster - metabolism Drosophila Proteins - genetics Drosophila Proteins - metabolism Electrophysiology Female Immunoenzyme Techniques Insects Kinases Larva - growth & development Larva - metabolism Male Mutation Mutation - genetics Neuromuscular Junction - physiology Neuropeptides - genetics Neuropeptides - metabolism Oligopeptides - genetics Oligopeptides - metabolism Presynaptic Terminals - metabolism Proteins Receptors, Cholecystokinin - genetics Receptors, Cholecystokinin - metabolism Signal Transduction Synapses - metabolism Synaptic Transmission - physiology |
| title | A neuropeptide signaling pathway regulates synaptic growth in Drosophila |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T19%3A40%3A38IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20neuropeptide%20signaling%20pathway%20regulates%20synaptic%20growth%20in%20Drosophila&rft.jtitle=The%20Journal%20of%20cell%20biology&rft.au=Chen,%20Xu&rft.date=2012-02-20&rft.volume=196&rft.issue=4&rft.spage=529&rft.epage=543&rft.pages=529-543&rft.issn=0021-9525&rft.eissn=1540-8140&rft.coden=JCLBA3&rft_id=info:doi/10.1083/jcb.201109044&rft_dat=%3Cproquest_pubme%3E2602840381%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=926413722&rft_id=info:pmid/22331845&rfr_iscdi=true |