Nucleoside Diphosphate Kinase, a Source of GTP, Is Required for Dynamin-Dependent Synaptic Vesicle Recycling
Nucleoside diphosphate kinase (NDK), an enzyme encoded by the Drosophila abnormal wing discs ( awd) or human nm23 tumor suppressor genes, generates nucleoside triphosphates from respective diphosphates. We demonstrate that NDK regulates synaptic vesicle internalization at the stage where function of...
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| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 2001-04, Vol.30 (1), p.197-210 |
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| creator | Krishnan, K.S Rikhy, Richa Rao, Sujata Shivalkar, Madhuri Mosko, Michael Narayanan, Radhakrishnan Etter, Paul Estes, Patricia S Ramaswami, Mani |
| description | Nucleoside diphosphate kinase (NDK), an enzyme encoded by the
Drosophila abnormal wing discs (
awd) or human
nm23 tumor suppressor genes, generates nucleoside triphosphates from respective diphosphates. We demonstrate that NDK regulates synaptic vesicle internalization at the stage where function of the dynamin GTPase is required.
awd mutations lower the temperature at which behavioral paralysis, synaptic failure, and blocked membrane internalization occur at dynamin-deficient,
shi
ts, mutant nerve terminals. Hypomorphic
awd alleles display
shi
ts-like defects. NDK is present at synapses and its enzymatic activity is essential for normal presynaptic function. We suggest a model in which dynamin activity in nerve terminals is highly dependent on NDK-mediated supply of GTP. This connection between NDK and membrane internalization further strengthens an emerging hypothesis that endocytosis, probably of activated growth factor receptors, is an important tumor suppressor activity in vivo. |
| doi_str_mv | 10.1016/S0896-6273(01)00273-2 |
| format | Article |
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Drosophila abnormal wing discs (
awd) or human
nm23 tumor suppressor genes, generates nucleoside triphosphates from respective diphosphates. We demonstrate that NDK regulates synaptic vesicle internalization at the stage where function of the dynamin GTPase is required.
awd mutations lower the temperature at which behavioral paralysis, synaptic failure, and blocked membrane internalization occur at dynamin-deficient,
shi
ts, mutant nerve terminals. Hypomorphic
awd alleles display
shi
ts-like defects. NDK is present at synapses and its enzymatic activity is essential for normal presynaptic function. We suggest a model in which dynamin activity in nerve terminals is highly dependent on NDK-mediated supply of GTP. This connection between NDK and membrane internalization further strengthens an emerging hypothesis that endocytosis, probably of activated growth factor receptors, is an important tumor suppressor activity in vivo.</description><identifier>ISSN: 0896-6273</identifier><identifier>EISSN: 1097-4199</identifier><identifier>DOI: 10.1016/S0896-6273(01)00273-2</identifier><identifier>PMID: 11343655</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alleles ; Animals ; Body Temperature - genetics ; Brain - metabolism ; Drosophila melanogaster - enzymology ; Drosophila melanogaster - genetics ; Drosophila Proteins ; dynamin ; Dynamins ; Endocytosis - genetics ; GTP ; GTP Phosphohydrolases - metabolism ; Guanosine Triphosphate - biosynthesis ; Insect Proteins - genetics ; Insect Proteins - metabolism ; Microscopy, Electron ; Monomeric GTP-Binding Proteins - genetics ; Monomeric GTP-Binding Proteins - metabolism ; Mutation - physiology ; Neoplasm Invasiveness - genetics ; NM23 Nucleoside Diphosphate Kinases ; nucleoside diphosphate kinase ; Nucleoside-Diphosphate Kinase - metabolism ; Paralysis - enzymology ; Paralysis - genetics ; Paralysis - physiopathology ; Phenotype ; Presynaptic Terminals - enzymology ; Presynaptic Terminals - ultrastructure ; Protein Transport - genetics ; Synaptic Vesicles - enzymology ; Synaptic Vesicles - ultrastructure ; Transcription Factors - genetics ; Transcription Factors - metabolism</subject><ispartof>Neuron (Cambridge, Mass.), 2001-04, Vol.30 (1), p.197-210</ispartof><rights>2001 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c557t-f0796739dd756e4988a19deca50fa1ef77c3b14bc1ea729bc2b3338e3e980e873</citedby><cites>FETCH-LOGICAL-c557t-f0796739dd756e4988a19deca50fa1ef77c3b14bc1ea729bc2b3338e3e980e873</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0896627301002732$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11343655$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krishnan, K.S</creatorcontrib><creatorcontrib>Rikhy, Richa</creatorcontrib><creatorcontrib>Rao, Sujata</creatorcontrib><creatorcontrib>Shivalkar, Madhuri</creatorcontrib><creatorcontrib>Mosko, Michael</creatorcontrib><creatorcontrib>Narayanan, Radhakrishnan</creatorcontrib><creatorcontrib>Etter, Paul</creatorcontrib><creatorcontrib>Estes, Patricia S</creatorcontrib><creatorcontrib>Ramaswami, Mani</creatorcontrib><title>Nucleoside Diphosphate Kinase, a Source of GTP, Is Required for Dynamin-Dependent Synaptic Vesicle Recycling</title><title>Neuron (Cambridge, Mass.)</title><addtitle>Neuron</addtitle><description>Nucleoside diphosphate kinase (NDK), an enzyme encoded by the
Drosophila abnormal wing discs (
awd) or human
nm23 tumor suppressor genes, generates nucleoside triphosphates from respective diphosphates. We demonstrate that NDK regulates synaptic vesicle internalization at the stage where function of the dynamin GTPase is required.
awd mutations lower the temperature at which behavioral paralysis, synaptic failure, and blocked membrane internalization occur at dynamin-deficient,
shi
ts, mutant nerve terminals. Hypomorphic
awd alleles display
shi
ts-like defects. NDK is present at synapses and its enzymatic activity is essential for normal presynaptic function. We suggest a model in which dynamin activity in nerve terminals is highly dependent on NDK-mediated supply of GTP. This connection between NDK and membrane internalization further strengthens an emerging hypothesis that endocytosis, probably of activated growth factor receptors, is an important tumor suppressor activity in vivo.</description><subject>Alleles</subject><subject>Animals</subject><subject>Body Temperature - genetics</subject><subject>Brain - metabolism</subject><subject>Drosophila melanogaster - enzymology</subject><subject>Drosophila melanogaster - genetics</subject><subject>Drosophila Proteins</subject><subject>dynamin</subject><subject>Dynamins</subject><subject>Endocytosis - genetics</subject><subject>GTP</subject><subject>GTP Phosphohydrolases - metabolism</subject><subject>Guanosine Triphosphate - biosynthesis</subject><subject>Insect Proteins - genetics</subject><subject>Insect Proteins - metabolism</subject><subject>Microscopy, Electron</subject><subject>Monomeric GTP-Binding Proteins - genetics</subject><subject>Monomeric GTP-Binding Proteins - metabolism</subject><subject>Mutation - physiology</subject><subject>Neoplasm Invasiveness - genetics</subject><subject>NM23 Nucleoside Diphosphate Kinases</subject><subject>nucleoside diphosphate kinase</subject><subject>Nucleoside-Diphosphate Kinase - metabolism</subject><subject>Paralysis - enzymology</subject><subject>Paralysis - genetics</subject><subject>Paralysis - physiopathology</subject><subject>Phenotype</subject><subject>Presynaptic Terminals - enzymology</subject><subject>Presynaptic Terminals - ultrastructure</subject><subject>Protein Transport - genetics</subject><subject>Synaptic Vesicles - enzymology</subject><subject>Synaptic Vesicles - ultrastructure</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><issn>0896-6273</issn><issn>1097-4199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhS0EokvhJ4B8QiA14Inj2D4h1IVSUQFiC1fLsSfUKBundoK0_x5vdwXHHkYzGn0zT3qPkOfA3gCD9u2GKd1WbS35KwavGStDVT8gK2BaVg1o_ZCs_iEn5EnOvxmDRmh4TE4AeMNbIVZk-LK4AWMOHuk6TDcxTzd2Rvo5jDbjGbV0E5fkkMaeXlx_O6OXmX7H2yUk9LSPia53o92GsVrjhKPHcaabspnm4OhPzKE8L7zbuSGMv56SR70dMj479lPy4-OH6_NP1dXXi8vz91eVE0LOVc-kbiXX3kvRYqOVsqA9OitYbwF7KR3voOkcoJW17lzdcc4VctSKoZL8lLw8_J1SvF0wz2YbssNhsCPGJRvJVC1K3QuCVAqKZQUUB9ClmHPC3kwpbG3aGWBmn4e5y8PszTYMzF0eZi_w4iiwdFv0_6-OARTg3QHA4sefgMlkF3B06IvDbjY-hnsk_gIIEJog</recordid><startdate>20010401</startdate><enddate>20010401</enddate><creator>Krishnan, K.S</creator><creator>Rikhy, Richa</creator><creator>Rao, Sujata</creator><creator>Shivalkar, Madhuri</creator><creator>Mosko, Michael</creator><creator>Narayanan, Radhakrishnan</creator><creator>Etter, Paul</creator><creator>Estes, Patricia S</creator><creator>Ramaswami, Mani</creator><general>Elsevier Inc</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>7TK</scope><scope>7X8</scope></search><sort><creationdate>20010401</creationdate><title>Nucleoside Diphosphate Kinase, a Source of GTP, Is Required for Dynamin-Dependent Synaptic Vesicle Recycling</title><author>Krishnan, K.S ; Rikhy, Richa ; Rao, Sujata ; Shivalkar, Madhuri ; Mosko, Michael ; Narayanan, Radhakrishnan ; Etter, Paul ; Estes, Patricia S ; Ramaswami, Mani</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-f0796739dd756e4988a19deca50fa1ef77c3b14bc1ea729bc2b3338e3e980e873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Alleles</topic><topic>Animals</topic><topic>Body Temperature - genetics</topic><topic>Brain - metabolism</topic><topic>Drosophila melanogaster - enzymology</topic><topic>Drosophila melanogaster - genetics</topic><topic>Drosophila Proteins</topic><topic>dynamin</topic><topic>Dynamins</topic><topic>Endocytosis - genetics</topic><topic>GTP</topic><topic>GTP Phosphohydrolases - metabolism</topic><topic>Guanosine Triphosphate - biosynthesis</topic><topic>Insect Proteins - genetics</topic><topic>Insect Proteins - metabolism</topic><topic>Microscopy, Electron</topic><topic>Monomeric GTP-Binding Proteins - genetics</topic><topic>Monomeric GTP-Binding Proteins - metabolism</topic><topic>Mutation - physiology</topic><topic>Neoplasm Invasiveness - genetics</topic><topic>NM23 Nucleoside Diphosphate Kinases</topic><topic>nucleoside diphosphate kinase</topic><topic>Nucleoside-Diphosphate Kinase - metabolism</topic><topic>Paralysis - enzymology</topic><topic>Paralysis - genetics</topic><topic>Paralysis - physiopathology</topic><topic>Phenotype</topic><topic>Presynaptic Terminals - enzymology</topic><topic>Presynaptic Terminals - ultrastructure</topic><topic>Protein Transport - genetics</topic><topic>Synaptic Vesicles - enzymology</topic><topic>Synaptic Vesicles - ultrastructure</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Krishnan, K.S</creatorcontrib><creatorcontrib>Rikhy, Richa</creatorcontrib><creatorcontrib>Rao, Sujata</creatorcontrib><creatorcontrib>Shivalkar, Madhuri</creatorcontrib><creatorcontrib>Mosko, Michael</creatorcontrib><creatorcontrib>Narayanan, Radhakrishnan</creatorcontrib><creatorcontrib>Etter, Paul</creatorcontrib><creatorcontrib>Estes, Patricia S</creatorcontrib><creatorcontrib>Ramaswami, Mani</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>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Neuron (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Krishnan, K.S</au><au>Rikhy, Richa</au><au>Rao, Sujata</au><au>Shivalkar, Madhuri</au><au>Mosko, Michael</au><au>Narayanan, Radhakrishnan</au><au>Etter, Paul</au><au>Estes, Patricia S</au><au>Ramaswami, Mani</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nucleoside Diphosphate Kinase, a Source of GTP, Is Required for Dynamin-Dependent Synaptic Vesicle Recycling</atitle><jtitle>Neuron (Cambridge, Mass.)</jtitle><addtitle>Neuron</addtitle><date>2001-04-01</date><risdate>2001</risdate><volume>30</volume><issue>1</issue><spage>197</spage><epage>210</epage><pages>197-210</pages><issn>0896-6273</issn><eissn>1097-4199</eissn><abstract>Nucleoside diphosphate kinase (NDK), an enzyme encoded by the
Drosophila abnormal wing discs (
awd) or human
nm23 tumor suppressor genes, generates nucleoside triphosphates from respective diphosphates. We demonstrate that NDK regulates synaptic vesicle internalization at the stage where function of the dynamin GTPase is required.
awd mutations lower the temperature at which behavioral paralysis, synaptic failure, and blocked membrane internalization occur at dynamin-deficient,
shi
ts, mutant nerve terminals. Hypomorphic
awd alleles display
shi
ts-like defects. NDK is present at synapses and its enzymatic activity is essential for normal presynaptic function. We suggest a model in which dynamin activity in nerve terminals is highly dependent on NDK-mediated supply of GTP. This connection between NDK and membrane internalization further strengthens an emerging hypothesis that endocytosis, probably of activated growth factor receptors, is an important tumor suppressor activity in vivo.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11343655</pmid><doi>10.1016/S0896-6273(01)00273-2</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0896-6273 |
| ispartof | Neuron (Cambridge, Mass.), 2001-04, Vol.30 (1), p.197-210 |
| issn | 0896-6273 1097-4199 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70825082 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Alleles Animals Body Temperature - genetics Brain - metabolism Drosophila melanogaster - enzymology Drosophila melanogaster - genetics Drosophila Proteins dynamin Dynamins Endocytosis - genetics GTP GTP Phosphohydrolases - metabolism Guanosine Triphosphate - biosynthesis Insect Proteins - genetics Insect Proteins - metabolism Microscopy, Electron Monomeric GTP-Binding Proteins - genetics Monomeric GTP-Binding Proteins - metabolism Mutation - physiology Neoplasm Invasiveness - genetics NM23 Nucleoside Diphosphate Kinases nucleoside diphosphate kinase Nucleoside-Diphosphate Kinase - metabolism Paralysis - enzymology Paralysis - genetics Paralysis - physiopathology Phenotype Presynaptic Terminals - enzymology Presynaptic Terminals - ultrastructure Protein Transport - genetics Synaptic Vesicles - enzymology Synaptic Vesicles - ultrastructure Transcription Factors - genetics Transcription Factors - metabolism |
| title | Nucleoside Diphosphate Kinase, a Source of GTP, Is Required for Dynamin-Dependent Synaptic Vesicle Recycling |
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