Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brain
The regulation of protein degradation is essential for maintaining the appropriate environment to coordinate complex cell signaling events and to promote cellular remodeling. The Autophagy linked FYVE protein (Alfy), previously identified as a molecular scaffold between the ubiquitinated cargo and t...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2016-09-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/14810 |
| _version_ | 1811236983386669056 |
|---|---|
| author | Joanna M Dragich Takaaki Kuwajima Megumi Hirose-Ikeda Michael S Yoon Evelien Eenjes Joan R Bosco Leora M Fox Alf H Lystad Tinmarla F Oo Olga Yarygina Tomohiro Mita Satoshi Waguri Yoshinobu Ichimura Masaaki Komatsu Anne Simonsen Robert E Burke Carol A Mason Ai Yamamoto |
| author_facet | Joanna M Dragich Takaaki Kuwajima Megumi Hirose-Ikeda Michael S Yoon Evelien Eenjes Joan R Bosco Leora M Fox Alf H Lystad Tinmarla F Oo Olga Yarygina Tomohiro Mita Satoshi Waguri Yoshinobu Ichimura Masaaki Komatsu Anne Simonsen Robert E Burke Carol A Mason Ai Yamamoto |
| author_sort | Joanna M Dragich |
| collection | DOAJ |
| description | The regulation of protein degradation is essential for maintaining the appropriate environment to coordinate complex cell signaling events and to promote cellular remodeling. The Autophagy linked FYVE protein (Alfy), previously identified as a molecular scaffold between the ubiquitinated cargo and the autophagic machinery, is highly expressed in the developing central nervous system, indicating that this pathway may have yet unexplored roles in neurodevelopment. To examine this possibility, we used mouse genetics to eliminate Alfy expression. We report that this evolutionarily conserved protein is required for the formation of axonal tracts throughout the brain and spinal cord, including the formation of the major forebrain commissures. Consistent with a phenotype reflecting a failure in axon guidance, the loss of Alfy in mice disrupts localization of glial guidepost cells, and attenuates axon outgrowth in response to Netrin-1. These findings further support the growing indication that macroautophagy plays a key role in the developing CNS. |
| first_indexed | 2024-04-12T12:18:07Z |
| format | Article |
| id | doaj.art-bebc1d11f6ea4e1fa0d10407c60fe990 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:18:07Z |
| publishDate | 2016-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-bebc1d11f6ea4e1fa0d10407c60fe9902022-12-22T03:33:23ZengeLife Sciences Publications LtdeLife2050-084X2016-09-01510.7554/eLife.14810Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brainJoanna M Dragich0Takaaki Kuwajima1Megumi Hirose-Ikeda2Michael S Yoon3Evelien Eenjes4Joan R Bosco5Leora M Fox6Alf H Lystad7Tinmarla F Oo8Olga Yarygina9Tomohiro Mita10https://orcid.org/0000-0002-3578-9801Satoshi Waguri11Yoshinobu Ichimura12Masaaki Komatsu13Anne Simonsen14Robert E Burke15Carol A Mason16https://orcid.org/0000-0001-6253-505XAi Yamamoto17https://orcid.org/0000-0002-7059-2449Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, United StatesDepartment of Pathology, College of Physicians and Surgeons, Columbia University, New York, United States; Department of Cell Biology, College of Physicians and Surgeons, Columbia University, New York, United StatesDepartment of Neurology, College of Physicians and Surgeons, Columbia University, New York, United StatesDepartment of Neurology, College of Physicians and Surgeons, Columbia University, New York, United StatesDepartment of Neurology, College of Physicians and Surgeons, Columbia University, New York, United StatesDepartment of Neurology, College of Physicians and Surgeons, Columbia University, New York, United StatesDepartment of Neurology, College of Physicians and Surgeons, Columbia University, New York, United States; Doctoral Program in Neurobiology and Behavior, Columbia University, New York, United StatesInstitute of Basic Medical Sciences, University of Oslo, Oslo, NorwayDepartment of Neurology, College of Physicians and Surgeons, Columbia University, New York, United StatesDepartment of Neurology, College of Physicians and Surgeons, Columbia University, New York, United StatesThe Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, JapanDepartment of Anatomy and Histology, Fukushima Medical University School of Medicine, Fukushima, JapanThe Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, JapanThe Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, JapanInstitute of Basic Medical Sciences, University of Oslo, Oslo, NorwayDepartment of Neurology, College of Physicians and Surgeons, Columbia University, New York, United States; Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, United States; Department of Cell Biology, College of Physicians and Surgeons, Columbia University, New York, United StatesDepartment of Pathology, College of Physicians and Surgeons, Columbia University, New York, United States; Department of Cell Biology, College of Physicians and Surgeons, Columbia University, New York, United States; Department of Neuroscience, College of Physicians and Surgeons, Columbia University, New York, United States; Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, United StatesDepartment of Neurology, College of Physicians and Surgeons, Columbia University, New York, United States; Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, United States; Department of Cell Biology, College of Physicians and Surgeons, Columbia University, New York, United StatesThe regulation of protein degradation is essential for maintaining the appropriate environment to coordinate complex cell signaling events and to promote cellular remodeling. The Autophagy linked FYVE protein (Alfy), previously identified as a molecular scaffold between the ubiquitinated cargo and the autophagic machinery, is highly expressed in the developing central nervous system, indicating that this pathway may have yet unexplored roles in neurodevelopment. To examine this possibility, we used mouse genetics to eliminate Alfy expression. We report that this evolutionarily conserved protein is required for the formation of axonal tracts throughout the brain and spinal cord, including the formation of the major forebrain commissures. Consistent with a phenotype reflecting a failure in axon guidance, the loss of Alfy in mice disrupts localization of glial guidepost cells, and attenuates axon outgrowth in response to Netrin-1. These findings further support the growing indication that macroautophagy plays a key role in the developing CNS.https://elifesciences.org/articles/14810AutophagyAlfyaxon guidancecorpus callosumneurodevelopmentWdfy3 |
| spellingShingle | Joanna M Dragich Takaaki Kuwajima Megumi Hirose-Ikeda Michael S Yoon Evelien Eenjes Joan R Bosco Leora M Fox Alf H Lystad Tinmarla F Oo Olga Yarygina Tomohiro Mita Satoshi Waguri Yoshinobu Ichimura Masaaki Komatsu Anne Simonsen Robert E Burke Carol A Mason Ai Yamamoto Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brain eLife Autophagy Alfy axon guidance corpus callosum neurodevelopment Wdfy3 |
| title | Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brain |
| title_full | Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brain |
| title_fullStr | Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brain |
| title_full_unstemmed | Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brain |
| title_short | Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brain |
| title_sort | autophagy linked fyve alfy wdfy3 is required for establishing neuronal connectivity in the mammalian brain |
| topic | Autophagy Alfy axon guidance corpus callosum neurodevelopment Wdfy3 |
| url | https://elifesciences.org/articles/14810 |
| work_keys_str_mv | AT joannamdragich autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT takaakikuwajima autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT megumihiroseikeda autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT michaelsyoon autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT evelieneenjes autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT joanrbosco autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT leoramfox autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT alfhlystad autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT tinmarlafoo autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT olgayarygina autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT tomohiromita autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT satoshiwaguri autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT yoshinobuichimura autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT masaakikomatsu autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT annesimonsen autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT roberteburke autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT carolamason autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain AT aiyamamoto autophagylinkedfyvealfywdfy3isrequiredforestablishingneuronalconnectivityinthemammalianbrain |