Involvement of IKAP in peripheral target innervation and in specific JNK and NGF signaling in developing PNS neurons
A splicing mutation in the ikbkap gene causes Familial Dysautonomia (FD), affecting the IKAP protein expression levels and proper development and function of the peripheral nervous system (PNS). Here we attempted to elucidate the role of IKAP in PNS development in the chick embryo and found that IKA...
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| description | A splicing mutation in the ikbkap gene causes Familial Dysautonomia (FD), affecting the IKAP protein expression levels and proper development and function of the peripheral nervous system (PNS). Here we attempted to elucidate the role of IKAP in PNS development in the chick embryo and found that IKAP is required for proper axonal outgrowth, branching, and peripheral target innervation. Moreover, we demonstrate that IKAP colocalizes with activated JNK (pJNK), dynein, and β-tubulin at the axon terminals of dorsal root ganglia (DRG) neurons, and may be involved in transport of specific target derived signals required for transcription of JNK and NGF responsive genes in the nucleus. These results suggest the novel role of IKAP in neuronal transport and specific signaling mediated transcription, and provide, for the first time, the basis for a molecular mechanism behind the FD phenotype. |
| doi_str_mv | 10.1371/journal.pone.0113428 |
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Here we attempted to elucidate the role of IKAP in PNS development in the chick embryo and found that IKAP is required for proper axonal outgrowth, branching, and peripheral target innervation. Moreover, we demonstrate that IKAP colocalizes with activated JNK (pJNK), dynein, and β-tubulin at the axon terminals of dorsal root ganglia (DRG) neurons, and may be involved in transport of specific target derived signals required for transcription of JNK and NGF responsive genes in the nucleus. These results suggest the novel role of IKAP in neuronal transport and specific signaling mediated transcription, and provide, for the first time, the basis for a molecular mechanism behind the FD phenotype.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0113428</identifier><identifier>PMID: 25409162</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Axon guidance ; Axonal transport ; Axons - metabolism ; Biology and Life Sciences ; Carrier Proteins - antagonists & inhibitors ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Cell adhesion & migration ; Cell Movement ; Cells, Cultured ; Chick Embryo ; Chickens ; Dorsal root ganglia ; Dynein ; Dyneins - metabolism ; Dysautonomia ; Dysautonomia, Familial - genetics ; Dysautonomia, Familial - pathology ; Ganglia ; Ganglia, Spinal - cytology ; Gene expression ; Genotype & phenotype ; Immunology ; Innervation ; JNK Mitogen-Activated Protein Kinases - metabolism ; JNK protein ; Kinases ; Laboratories ; Life sciences ; Microscopy, Fluorescence ; Mutation ; Nerve growth factor ; Nerve Growth Factor - metabolism ; Nervous system ; Neurogenesis ; Neurons ; Neurons - cytology ; Neurons - metabolism ; Neuropathology ; Neurosciences ; Peripheral nervous system ; Peripheral Nervous System - growth & development ; Peripheral Nervous System - pathology ; Precision medicine ; Presynapse ; Proteins ; RNA Interference ; RNA, Small Interfering - metabolism ; Rodents ; Signal Transduction ; Signaling ; Splicing ; Stem cells ; Transcription ; Transfer RNA ; Transport buildings, stations and terminals ; Tubulin ; Tubulin - chemistry ; Tubulin - metabolism</subject><ispartof>PloS one, 2014-11, Vol.9 (11), p.e113428-e113428</ispartof><rights>2014 Abashidze et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Abashidze et al 2014 Abashidze et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-e550b3df552bdeb84818a84f0dcaefb60ff835cb5973310d3909fbadcad0b2e63</citedby><cites>FETCH-LOGICAL-c526t-e550b3df552bdeb84818a84f0dcaefb60ff835cb5973310d3909fbadcad0b2e63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237409/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237409/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25409162$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Yang, Yanmin</contributor><creatorcontrib>Abashidze, Anastasia</creatorcontrib><creatorcontrib>Gold, Veronica</creatorcontrib><creatorcontrib>Anavi, Yaron</creatorcontrib><creatorcontrib>Greenspan, Hayit</creatorcontrib><creatorcontrib>Weil, Miguel</creatorcontrib><title>Involvement of IKAP in peripheral target innervation and in specific JNK and NGF signaling in developing PNS neurons</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>A splicing mutation in the ikbkap gene causes Familial Dysautonomia (FD), affecting the IKAP protein expression levels and proper development and function of the peripheral nervous system (PNS). Here we attempted to elucidate the role of IKAP in PNS development in the chick embryo and found that IKAP is required for proper axonal outgrowth, branching, and peripheral target innervation. Moreover, we demonstrate that IKAP colocalizes with activated JNK (pJNK), dynein, and β-tubulin at the axon terminals of dorsal root ganglia (DRG) neurons, and may be involved in transport of specific target derived signals required for transcription of JNK and NGF responsive genes in the nucleus. These results suggest the novel role of IKAP in neuronal transport and specific signaling mediated transcription, and provide, for the first time, the basis for a molecular mechanism behind the FD phenotype.</description><subject>Animals</subject><subject>Axon guidance</subject><subject>Axonal transport</subject><subject>Axons - metabolism</subject><subject>Biology and Life Sciences</subject><subject>Carrier Proteins - antagonists & inhibitors</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell adhesion & migration</subject><subject>Cell Movement</subject><subject>Cells, Cultured</subject><subject>Chick Embryo</subject><subject>Chickens</subject><subject>Dorsal root ganglia</subject><subject>Dynein</subject><subject>Dyneins - metabolism</subject><subject>Dysautonomia</subject><subject>Dysautonomia, Familial - genetics</subject><subject>Dysautonomia, Familial - pathology</subject><subject>Ganglia</subject><subject>Ganglia, Spinal - 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metabolism</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Splicing</subject><subject>Stem cells</subject><subject>Transcription</subject><subject>Transfer RNA</subject><subject>Transport buildings, stations and terminals</subject><subject>Tubulin</subject><subject>Tubulin - chemistry</subject><subject>Tubulin - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUk1v1DAQjRCIloV_gCASl1528UfsJBekqqJlabVUAs6WY49Tr7J2sJOV-Pd1dtOqRZxsz7x582b8suw9RitMS_x568fgZLfqvYMVwpgWpHqRneKakiUniL58cj_J3sS4RYjRivPX2QlhBaoxJ6fZsHZ73-1hB27IvcnX1-e3uXV5D8H2dxBklw8ytDCkoIOwl4P1LpdOT6DYg7LGqvz75voQ21xd5tG2SZZ17YTQsIfO99PrdvMzdzAG7-Lb7JWRXYR387nIfl9-_XXxbXnz42p9cX6zVIzwYQmMoYZqwxhpNDRVUeFKVoVBWkkwDUfGVJSphtUlpRhpWqPaNDJlNWoIcLrIPh55-85HMS8sijQ4xyUqaJ0Q6yNCe7kVfbA7Gf4KL604BHxohQyDVR0I4IqqUvGGJQ2gQWKC6zrxYGWAFypxfZm7jc0OtEobTet7Rvo84-ydaP1eFISW6T8SwdlMEPyfEeIgdjYq6DrpwI8H3SUqMUn4RfbpH-j_pyuOKBV8jAHMoxiMxGSihyoxmUjMJkplH54O8lj04Bp6D6uoxsc</recordid><startdate>20141119</startdate><enddate>20141119</enddate><creator>Abashidze, Anastasia</creator><creator>Gold, Veronica</creator><creator>Anavi, Yaron</creator><creator>Greenspan, Hayit</creator><creator>Weil, Miguel</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20141119</creationdate><title>Involvement of IKAP in peripheral target innervation and in specific JNK and NGF signaling in developing PNS neurons</title><author>Abashidze, Anastasia ; Gold, Veronica ; Anavi, Yaron ; Greenspan, Hayit ; Weil, Miguel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-e550b3df552bdeb84818a84f0dcaefb60ff835cb5973310d3909fbadcad0b2e63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Axon guidance</topic><topic>Axonal transport</topic><topic>Axons - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abashidze, Anastasia</au><au>Gold, Veronica</au><au>Anavi, Yaron</au><au>Greenspan, Hayit</au><au>Weil, Miguel</au><au>Yang, Yanmin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Involvement of IKAP in peripheral target innervation and in specific JNK and NGF signaling in developing PNS neurons</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-11-19</date><risdate>2014</risdate><volume>9</volume><issue>11</issue><spage>e113428</spage><epage>e113428</epage><pages>e113428-e113428</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>A splicing mutation in the ikbkap gene causes Familial Dysautonomia (FD), affecting the IKAP protein expression levels and proper development and function of the peripheral nervous system (PNS). Here we attempted to elucidate the role of IKAP in PNS development in the chick embryo and found that IKAP is required for proper axonal outgrowth, branching, and peripheral target innervation. Moreover, we demonstrate that IKAP colocalizes with activated JNK (pJNK), dynein, and β-tubulin at the axon terminals of dorsal root ganglia (DRG) neurons, and may be involved in transport of specific target derived signals required for transcription of JNK and NGF responsive genes in the nucleus. These results suggest the novel role of IKAP in neuronal transport and specific signaling mediated transcription, and provide, for the first time, the basis for a molecular mechanism behind the FD phenotype.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25409162</pmid><doi>10.1371/journal.pone.0113428</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Axon guidance Axonal transport Axons - metabolism Biology and Life Sciences Carrier Proteins - antagonists & inhibitors Carrier Proteins - genetics Carrier Proteins - metabolism Cell adhesion & migration Cell Movement Cells, Cultured Chick Embryo Chickens Dorsal root ganglia Dynein Dyneins - metabolism Dysautonomia Dysautonomia, Familial - genetics Dysautonomia, Familial - pathology Ganglia Ganglia, Spinal - cytology Gene expression Genotype & phenotype Immunology Innervation JNK Mitogen-Activated Protein Kinases - metabolism JNK protein Kinases Laboratories Life sciences Microscopy, Fluorescence Mutation Nerve growth factor Nerve Growth Factor - metabolism Nervous system Neurogenesis Neurons Neurons - cytology Neurons - metabolism Neuropathology Neurosciences Peripheral nervous system Peripheral Nervous System - growth & development Peripheral Nervous System - pathology Precision medicine Presynapse Proteins RNA Interference RNA, Small Interfering - metabolism Rodents Signal Transduction Signaling Splicing Stem cells Transcription Transfer RNA Transport buildings, stations and terminals Tubulin Tubulin - chemistry Tubulin - metabolism |
| title | Involvement of IKAP in peripheral target innervation and in specific JNK and NGF signaling in developing PNS neurons |
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