MICALs, a Family of Conserved Flavoprotein Oxidoreductases, Function in Plexin-Mediated Axonal Repulsion
Members of the semaphorin family of secreted and transmembrane proteins utilize plexins as neuronal receptors to signal repulsive axon guidance. It remains unknown how plexin proteins are directly linked to the regulation of cytoskeletal dynamics. Here, we show that Drosophila MICAL, a large, multid...
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description | Members of the semaphorin family of secreted and transmembrane proteins utilize plexins as neuronal receptors to signal repulsive axon guidance. It remains unknown how plexin proteins are directly linked to the regulation of cytoskeletal dynamics. Here, we show that
Drosophila MICAL, a large, multidomain, cytosolic protein expressed in axons, interacts with the neuronal plexin A (PlexA) receptor and is required for Semaphorin 1a (Sema-1a)-PlexA-mediated repulsive axon guidance. In addition to containing several domains known to interact with cytoskeletal components, MICAL has a flavoprotein monooxygenase domain, the integrity of which is required for Sema-1a-PlexA repulsive axon guidance. Vertebrate orthologs of
Drosophila MICAL are neuronally expressed and also interact with vertebrate plexins, and monooxygenase inhibitors abrogate semaphorin-mediated axonal repulsion. These results suggest a novel role for oxidoreductases in repulsive neuronal guidance. |
doi_str_mv | 10.1016/S0092-8674(02)00794-8 |
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Drosophila MICAL, a large, multidomain, cytosolic protein expressed in axons, interacts with the neuronal plexin A (PlexA) receptor and is required for Semaphorin 1a (Sema-1a)-PlexA-mediated repulsive axon guidance. In addition to containing several domains known to interact with cytoskeletal components, MICAL has a flavoprotein monooxygenase domain, the integrity of which is required for Sema-1a-PlexA repulsive axon guidance. Vertebrate orthologs of
Drosophila MICAL are neuronally expressed and also interact with vertebrate plexins, and monooxygenase inhibitors abrogate semaphorin-mediated axonal repulsion. These results suggest a novel role for oxidoreductases in repulsive neuronal guidance.</description><identifier>ISSN: 0092-8674</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/S0092-8674(02)00794-8</identifier><identifier>PMID: 12110185</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Actins - metabolism ; Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Animals ; Axons - enzymology ; Axons - metabolism ; Binding Sites ; Blotting, Western ; Cell Adhesion Molecules - genetics ; Cell Adhesion Molecules - metabolism ; Cell Adhesion Molecules, Neuronal - genetics ; Cell Adhesion Molecules, Neuronal - metabolism ; Conserved Sequence ; Cytoskeletal Proteins - antagonists & inhibitors ; Cytoskeletal Proteins - chemistry ; Cytoskeletal Proteins - genetics ; Cytoskeletal Proteins - metabolism ; Cytoskeleton - metabolism ; Drosophila melanogaster - enzymology ; Drosophila melanogaster - genetics ; Drosophila Proteins - genetics ; Drosophila Proteins - metabolism ; Flavin-Adenine Dinucleotide - metabolism ; Flavoproteins - antagonists & inhibitors ; Flavoproteins - chemistry ; Flavoproteins - genetics ; Flavoproteins - metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; LIM Domain Proteins ; Molecular Sequence Data ; Mutation ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Oxidoreductases - antagonists & inhibitors ; Oxidoreductases - chemistry ; Oxidoreductases - genetics ; Oxidoreductases - metabolism ; Phenotype ; Protein Binding ; Protein Structure, Tertiary ; Semaphorins ; Sequence Homology, Amino Acid ; Signal Transduction</subject><ispartof>Cell, 2002-06, Vol.109 (7), p.887-900</ispartof><rights>2002 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c557t-410b98186510948f7f9b57b774d680f548e981abdae797ec9da7dfc0a12718033</citedby><cites>FETCH-LOGICAL-c557t-410b98186510948f7f9b57b774d680f548e981abdae797ec9da7dfc0a12718033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0092867402007948$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12110185$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Terman, Jonathan R.</creatorcontrib><creatorcontrib>Mao, Tianyi</creatorcontrib><creatorcontrib>Pasterkamp, R.Jeroen</creatorcontrib><creatorcontrib>Yu, Hung-Hsiang</creatorcontrib><creatorcontrib>Kolodkin, Alex L.</creatorcontrib><title>MICALs, a Family of Conserved Flavoprotein Oxidoreductases, Function in Plexin-Mediated Axonal Repulsion</title><title>Cell</title><addtitle>Cell</addtitle><description>Members of the semaphorin family of secreted and transmembrane proteins utilize plexins as neuronal receptors to signal repulsive axon guidance. It remains unknown how plexin proteins are directly linked to the regulation of cytoskeletal dynamics. Here, we show that
Drosophila MICAL, a large, multidomain, cytosolic protein expressed in axons, interacts with the neuronal plexin A (PlexA) receptor and is required for Semaphorin 1a (Sema-1a)-PlexA-mediated repulsive axon guidance. In addition to containing several domains known to interact with cytoskeletal components, MICAL has a flavoprotein monooxygenase domain, the integrity of which is required for Sema-1a-PlexA repulsive axon guidance. Vertebrate orthologs of
Drosophila MICAL are neuronally expressed and also interact with vertebrate plexins, and monooxygenase inhibitors abrogate semaphorin-mediated axonal repulsion. These results suggest a novel role for oxidoreductases in repulsive neuronal guidance.</description><subject>Actins - metabolism</subject><subject>Adaptor Proteins, Signal Transducing</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Axons - enzymology</subject><subject>Axons - metabolism</subject><subject>Binding Sites</subject><subject>Blotting, Western</subject><subject>Cell Adhesion Molecules - genetics</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cell Adhesion Molecules, Neuronal - genetics</subject><subject>Cell Adhesion Molecules, Neuronal - metabolism</subject><subject>Conserved Sequence</subject><subject>Cytoskeletal Proteins - antagonists & inhibitors</subject><subject>Cytoskeletal Proteins - chemistry</subject><subject>Cytoskeletal Proteins - genetics</subject><subject>Cytoskeletal Proteins - metabolism</subject><subject>Cytoskeleton - metabolism</subject><subject>Drosophila melanogaster - enzymology</subject><subject>Drosophila melanogaster - genetics</subject><subject>Drosophila Proteins - genetics</subject><subject>Drosophila Proteins - metabolism</subject><subject>Flavin-Adenine Dinucleotide - metabolism</subject><subject>Flavoproteins - antagonists & inhibitors</subject><subject>Flavoproteins - chemistry</subject><subject>Flavoproteins - genetics</subject><subject>Flavoproteins - metabolism</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>LIM Domain Proteins</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Oxidoreductases - antagonists & inhibitors</subject><subject>Oxidoreductases - chemistry</subject><subject>Oxidoreductases - genetics</subject><subject>Oxidoreductases - metabolism</subject><subject>Phenotype</subject><subject>Protein Binding</subject><subject>Protein Structure, Tertiary</subject><subject>Semaphorins</subject><subject>Sequence Homology, Amino Acid</subject><subject>Signal Transduction</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtPwzAQhC0EgvL4CaCcEEgE1iGOnROqKgpIrUA8zpZjb4RRGhc7qcq_x6UVHDn5sN_sjmcIOaZwSYEWVy8AZZaKgudnkJ0D8DJPxRYZUCh5mlOebZPBL7JH9kP4AADBGNslezSjcYlgA_I-fRgNJ-EiUclYzWzzlbg6Gbk2oF-gScaNWri5dx3aNnlcWuM8ml53KmDUjPtWd9a1SRw-Nbi0bTpFY1UXlcOla1WTPOO8b0JkDslOrZqAR5v3gLyNb19H9-nk8W5lIdWM8S46h6oUVBQsfiQXNa_LivGK89wUAmqWC4xjVRmFvOSoS6O4qTUomnEq4Pr6gJyu90bXnz2GTs5s0Ng0qkXXB8lpCRGl_4JU5AXNGUSQrUHtXQgeazn3dqb8l6QgV13Iny7kKmgJmfzpQoqoO9kc6KsZmj_VJvwI3KwBjHksLHoZtMVWxwg96k4aZ_858Q3hEZhY</recordid><startdate>20020628</startdate><enddate>20020628</enddate><creator>Terman, Jonathan R.</creator><creator>Mao, Tianyi</creator><creator>Pasterkamp, R.Jeroen</creator><creator>Yu, Hung-Hsiang</creator><creator>Kolodkin, Alex L.</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>7SS</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>20020628</creationdate><title>MICALs, a Family of Conserved Flavoprotein Oxidoreductases, Function in Plexin-Mediated Axonal Repulsion</title><author>Terman, Jonathan R. ; Mao, Tianyi ; Pasterkamp, R.Jeroen ; Yu, Hung-Hsiang ; Kolodkin, Alex L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-410b98186510948f7f9b57b774d680f548e981abdae797ec9da7dfc0a12718033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Actins - metabolism</topic><topic>Adaptor Proteins, Signal Transducing</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Axons - enzymology</topic><topic>Axons - metabolism</topic><topic>Binding Sites</topic><topic>Blotting, Western</topic><topic>Cell Adhesion Molecules - genetics</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>Cell Adhesion Molecules, Neuronal - genetics</topic><topic>Cell Adhesion Molecules, Neuronal - metabolism</topic><topic>Conserved Sequence</topic><topic>Cytoskeletal Proteins - antagonists & inhibitors</topic><topic>Cytoskeletal Proteins - chemistry</topic><topic>Cytoskeletal Proteins - genetics</topic><topic>Cytoskeletal Proteins - metabolism</topic><topic>Cytoskeleton - metabolism</topic><topic>Drosophila melanogaster - enzymology</topic><topic>Drosophila melanogaster - genetics</topic><topic>Drosophila Proteins - genetics</topic><topic>Drosophila Proteins - metabolism</topic><topic>Flavin-Adenine Dinucleotide - metabolism</topic><topic>Flavoproteins - antagonists & inhibitors</topic><topic>Flavoproteins - chemistry</topic><topic>Flavoproteins - genetics</topic><topic>Flavoproteins - metabolism</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>LIM Domain Proteins</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Oxidoreductases - antagonists & inhibitors</topic><topic>Oxidoreductases - chemistry</topic><topic>Oxidoreductases - genetics</topic><topic>Oxidoreductases - metabolism</topic><topic>Phenotype</topic><topic>Protein Binding</topic><topic>Protein Structure, Tertiary</topic><topic>Semaphorins</topic><topic>Sequence Homology, Amino Acid</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Terman, Jonathan R.</creatorcontrib><creatorcontrib>Mao, Tianyi</creatorcontrib><creatorcontrib>Pasterkamp, R.Jeroen</creatorcontrib><creatorcontrib>Yu, Hung-Hsiang</creatorcontrib><creatorcontrib>Kolodkin, Alex L.</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>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Terman, Jonathan R.</au><au>Mao, Tianyi</au><au>Pasterkamp, R.Jeroen</au><au>Yu, Hung-Hsiang</au><au>Kolodkin, Alex L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MICALs, a Family of Conserved Flavoprotein Oxidoreductases, Function in Plexin-Mediated Axonal Repulsion</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2002-06-28</date><risdate>2002</risdate><volume>109</volume><issue>7</issue><spage>887</spage><epage>900</epage><pages>887-900</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>Members of the semaphorin family of secreted and transmembrane proteins utilize plexins as neuronal receptors to signal repulsive axon guidance. It remains unknown how plexin proteins are directly linked to the regulation of cytoskeletal dynamics. Here, we show that
Drosophila MICAL, a large, multidomain, cytosolic protein expressed in axons, interacts with the neuronal plexin A (PlexA) receptor and is required for Semaphorin 1a (Sema-1a)-PlexA-mediated repulsive axon guidance. In addition to containing several domains known to interact with cytoskeletal components, MICAL has a flavoprotein monooxygenase domain, the integrity of which is required for Sema-1a-PlexA repulsive axon guidance. Vertebrate orthologs of
Drosophila MICAL are neuronally expressed and also interact with vertebrate plexins, and monooxygenase inhibitors abrogate semaphorin-mediated axonal repulsion. These results suggest a novel role for oxidoreductases in repulsive neuronal guidance.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12110185</pmid><doi>10.1016/S0092-8674(02)00794-8</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Actins - metabolism Adaptor Proteins, Signal Transducing Amino Acid Sequence Animals Axons - enzymology Axons - metabolism Binding Sites Blotting, Western Cell Adhesion Molecules - genetics Cell Adhesion Molecules - metabolism Cell Adhesion Molecules, Neuronal - genetics Cell Adhesion Molecules, Neuronal - metabolism Conserved Sequence Cytoskeletal Proteins - antagonists & inhibitors Cytoskeletal Proteins - chemistry Cytoskeletal Proteins - genetics Cytoskeletal Proteins - metabolism Cytoskeleton - metabolism Drosophila melanogaster - enzymology Drosophila melanogaster - genetics Drosophila Proteins - genetics Drosophila Proteins - metabolism Flavin-Adenine Dinucleotide - metabolism Flavoproteins - antagonists & inhibitors Flavoproteins - chemistry Flavoproteins - genetics Flavoproteins - metabolism Humans Intracellular Signaling Peptides and Proteins LIM Domain Proteins Molecular Sequence Data Mutation Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Oxidoreductases - antagonists & inhibitors Oxidoreductases - chemistry Oxidoreductases - genetics Oxidoreductases - metabolism Phenotype Protein Binding Protein Structure, Tertiary Semaphorins Sequence Homology, Amino Acid Signal Transduction |
title | MICALs, a Family of Conserved Flavoprotein Oxidoreductases, Function in Plexin-Mediated Axonal Repulsion |
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