Presenilin/γ-secretase-dependent epha3 processing mediates axon elongation through non-muscle myosin IIA

EphA/ephrin signaling regulates axon growth and guidance of neurons, but whether this process occurs also independently of ephrins is unclear. We show that presenilin-1 (PS1)/γ-secretase is required for axon growth in the developing mouse brain. PS1/γ-secretase mediates axon growth by inhibiting Rho...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Hauptverfasser:	Javier, Miriam, Marco, Sergi, Rocandio, Daniel, Pons Vizcarra, Maria, Janes, Peter W, Lackmann, Martin, Egea, Joaquim, Saura Antolín, Carlos
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Axons Cells, Cultured Humans Mice Nonmuscle Myosin Type IIA Presenilin-1 Receptor, EphA3 Rhoa GTP-Binding Protein Signal Transduction
Online-Zugang:	Volltext bestellen
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

container_end_page
container_issue
container_start_page
container_title
container_volume
creator	Javier, Miriam Marco, Sergi Rocandio, Daniel Pons Vizcarra, Maria Janes, Peter W Lackmann, Martin Egea, Joaquim Saura Antolín, Carlos
description	EphA/ephrin signaling regulates axon growth and guidance of neurons, but whether this process occurs also independently of ephrins is unclear. We show that presenilin-1 (PS1)/γ-secretase is required for axon growth in the developing mouse brain. PS1/γ-secretase mediates axon growth by inhibiting RhoA signaling and cleaving EphA3 independently of ligand to generate an intracellular domain (ICD) fragment that reverses axon defects in PS1/γ-secretase-and EphA3-deficient hippocampal neurons. Proteomic analysis revealed that EphA3 ICD binds to non-muscle myosin IIA (NMIIA) and increases its phosphorylation (Ser1943), which promotes NMIIA filament disassembly and cytoskeleton rearrangement. PS1/γ-secretase-deficient neurons show decreased phosphorylated NMIIA and NMIIA/actin colocalization. Moreover, pharmacological NMII inhibition reverses axon retraction in PS-deficient neurons suggesting that NMIIA mediates PS/EphA3-dependent axon elongation. In conclusion, PS/γ-secretase-dependent EphA3 cleavage mediates axon growth by regulating filament assembly through RhoA signaling and NMIIA, suggesting opposite roles of EphA3 on inhibiting (ligand-dependent) and promoting (receptor processing) axon growth in developing neurons.
format	Article
fullrecord	<record><control><sourceid>csuc_XX2</sourceid><recordid>TN_cdi_csuc_recercat_oai_recercat_cat_2072_505385</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>oai_recercat_cat_2072_505385</sourcerecordid><originalsourceid>FETCH-csuc_recercat_oai_recercat_cat_2072_5053853</originalsourceid><addsrcrecordid>eNqdizEKwkAQRdNYiHqHuUAwJgRtRRTTWdiHYfNNFjazYWcDei7v4ZmMINhbPP77xZsn9hKgEOusrF_PVGECIivSBgOkgUTC0HFBQ_AGqlZa6tFYjlDiuxeC89JytJPGLvix7Ui8pP2oxoH6h58aqqr9Mpnd2ClW310km9PxejinRkdTBxgEw7H2bH_nQ55t87rMymJXFv80b8EzTwU</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Presenilin/γ-secretase-dependent epha3 processing mediates axon elongation through non-muscle myosin IIA</title><source>Recercat</source><creator>Javier, Miriam ; Marco, Sergi ; Rocandio, Daniel ; Pons Vizcarra, Maria ; Janes, Peter W ; Lackmann, Martin ; Egea, Joaquim ; Saura Antolín, Carlos</creator><creatorcontrib>Javier, Miriam ; Marco, Sergi ; Rocandio, Daniel ; Pons Vizcarra, Maria ; Janes, Peter W ; Lackmann, Martin ; Egea, Joaquim ; Saura Antolín, Carlos</creatorcontrib><description>EphA/ephrin signaling regulates axon growth and guidance of neurons, but whether this process occurs also independently of ephrins is unclear. We show that presenilin-1 (PS1)/γ-secretase is required for axon growth in the developing mouse brain. PS1/γ-secretase mediates axon growth by inhibiting RhoA signaling and cleaving EphA3 independently of ligand to generate an intracellular domain (ICD) fragment that reverses axon defects in PS1/γ-secretase-and EphA3-deficient hippocampal neurons. Proteomic analysis revealed that EphA3 ICD binds to non-muscle myosin IIA (NMIIA) and increases its phosphorylation (Ser1943), which promotes NMIIA filament disassembly and cytoskeleton rearrangement. PS1/γ-secretase-deficient neurons show decreased phosphorylated NMIIA and NMIIA/actin colocalization. Moreover, pharmacological NMII inhibition reverses axon retraction in PS-deficient neurons suggesting that NMIIA mediates PS/EphA3-dependent axon elongation. In conclusion, PS/γ-secretase-dependent EphA3 cleavage mediates axon growth by regulating filament assembly through RhoA signaling and NMIIA, suggesting opposite roles of EphA3 on inhibiting (ligand-dependent) and promoting (receptor processing) axon growth in developing neurons.</description><language>eng</language><subject>Animals ; Axons ; Cells, Cultured ; Humans ; Mice ; Nonmuscle Myosin Type IIA ; Presenilin-1 ; Receptor, EphA3 ; Rhoa GTP-Binding Protein ; Signal Transduction</subject><creationdate>2019</creationdate><rights>open access Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. https://creativecommons.org/licenses/by/4.0</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,776,881,26951</link.rule.ids><linktorsrc>$$Uhttps://recercat.cat/handle/2072/505385$$EView_record_in_Consorci_de_Serveis_Universitaris_de_Catalunya_(CSUC)$$FView_record_in_$$GConsorci_de_Serveis_Universitaris_de_Catalunya_(CSUC)$$Hfree_for_read</linktorsrc></links><search><creatorcontrib>Javier, Miriam</creatorcontrib><creatorcontrib>Marco, Sergi</creatorcontrib><creatorcontrib>Rocandio, Daniel</creatorcontrib><creatorcontrib>Pons Vizcarra, Maria</creatorcontrib><creatorcontrib>Janes, Peter W</creatorcontrib><creatorcontrib>Lackmann, Martin</creatorcontrib><creatorcontrib>Egea, Joaquim</creatorcontrib><creatorcontrib>Saura Antolín, Carlos</creatorcontrib><title>Presenilin/γ-secretase-dependent epha3 processing mediates axon elongation through non-muscle myosin IIA</title><description>EphA/ephrin signaling regulates axon growth and guidance of neurons, but whether this process occurs also independently of ephrins is unclear. We show that presenilin-1 (PS1)/γ-secretase is required for axon growth in the developing mouse brain. PS1/γ-secretase mediates axon growth by inhibiting RhoA signaling and cleaving EphA3 independently of ligand to generate an intracellular domain (ICD) fragment that reverses axon defects in PS1/γ-secretase-and EphA3-deficient hippocampal neurons. Proteomic analysis revealed that EphA3 ICD binds to non-muscle myosin IIA (NMIIA) and increases its phosphorylation (Ser1943), which promotes NMIIA filament disassembly and cytoskeleton rearrangement. PS1/γ-secretase-deficient neurons show decreased phosphorylated NMIIA and NMIIA/actin colocalization. Moreover, pharmacological NMII inhibition reverses axon retraction in PS-deficient neurons suggesting that NMIIA mediates PS/EphA3-dependent axon elongation. In conclusion, PS/γ-secretase-dependent EphA3 cleavage mediates axon growth by regulating filament assembly through RhoA signaling and NMIIA, suggesting opposite roles of EphA3 on inhibiting (ligand-dependent) and promoting (receptor processing) axon growth in developing neurons.</description><subject>Animals</subject><subject>Axons</subject><subject>Cells, Cultured</subject><subject>Humans</subject><subject>Mice</subject><subject>Nonmuscle Myosin Type IIA</subject><subject>Presenilin-1</subject><subject>Receptor, EphA3</subject><subject>Rhoa GTP-Binding Protein</subject><subject>Signal Transduction</subject><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>XX2</sourceid><recordid>eNqdizEKwkAQRdNYiHqHuUAwJgRtRRTTWdiHYfNNFjazYWcDei7v4ZmMINhbPP77xZsn9hKgEOusrF_PVGECIivSBgOkgUTC0HFBQ_AGqlZa6tFYjlDiuxeC89JytJPGLvix7Ui8pP2oxoH6h58aqqr9Mpnd2ClW310km9PxejinRkdTBxgEw7H2bH_nQ55t87rMymJXFv80b8EzTwU</recordid><startdate>2019</startdate><enddate>2019</enddate><creator>Javier, Miriam</creator><creator>Marco, Sergi</creator><creator>Rocandio, Daniel</creator><creator>Pons Vizcarra, Maria</creator><creator>Janes, Peter W</creator><creator>Lackmann, Martin</creator><creator>Egea, Joaquim</creator><creator>Saura Antolín, Carlos</creator><scope>XX2</scope></search><sort><creationdate>2019</creationdate><title>Presenilin/γ-secretase-dependent epha3 processing mediates axon elongation through non-muscle myosin IIA</title><author>Javier, Miriam ; Marco, Sergi ; Rocandio, Daniel ; Pons Vizcarra, Maria ; Janes, Peter W ; Lackmann, Martin ; Egea, Joaquim ; Saura Antolín, Carlos</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-csuc_recercat_oai_recercat_cat_2072_5053853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Axons</topic><topic>Cells, Cultured</topic><topic>Humans</topic><topic>Mice</topic><topic>Nonmuscle Myosin Type IIA</topic><topic>Presenilin-1</topic><topic>Receptor, EphA3</topic><topic>Rhoa GTP-Binding Protein</topic><topic>Signal Transduction</topic><toplevel>online_resources</toplevel><creatorcontrib>Javier, Miriam</creatorcontrib><creatorcontrib>Marco, Sergi</creatorcontrib><creatorcontrib>Rocandio, Daniel</creatorcontrib><creatorcontrib>Pons Vizcarra, Maria</creatorcontrib><creatorcontrib>Janes, Peter W</creatorcontrib><creatorcontrib>Lackmann, Martin</creatorcontrib><creatorcontrib>Egea, Joaquim</creatorcontrib><creatorcontrib>Saura Antolín, Carlos</creatorcontrib><collection>Recercat</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Javier, Miriam</au><au>Marco, Sergi</au><au>Rocandio, Daniel</au><au>Pons Vizcarra, Maria</au><au>Janes, Peter W</au><au>Lackmann, Martin</au><au>Egea, Joaquim</au><au>Saura Antolín, Carlos</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Presenilin/γ-secretase-dependent epha3 processing mediates axon elongation through non-muscle myosin IIA</atitle><date>2019</date><risdate>2019</risdate><abstract>EphA/ephrin signaling regulates axon growth and guidance of neurons, but whether this process occurs also independently of ephrins is unclear. We show that presenilin-1 (PS1)/γ-secretase is required for axon growth in the developing mouse brain. PS1/γ-secretase mediates axon growth by inhibiting RhoA signaling and cleaving EphA3 independently of ligand to generate an intracellular domain (ICD) fragment that reverses axon defects in PS1/γ-secretase-and EphA3-deficient hippocampal neurons. Proteomic analysis revealed that EphA3 ICD binds to non-muscle myosin IIA (NMIIA) and increases its phosphorylation (Ser1943), which promotes NMIIA filament disassembly and cytoskeleton rearrangement. PS1/γ-secretase-deficient neurons show decreased phosphorylated NMIIA and NMIIA/actin colocalization. Moreover, pharmacological NMII inhibition reverses axon retraction in PS-deficient neurons suggesting that NMIIA mediates PS/EphA3-dependent axon elongation. In conclusion, PS/γ-secretase-dependent EphA3 cleavage mediates axon growth by regulating filament assembly through RhoA signaling and NMIIA, suggesting opposite roles of EphA3 on inhibiting (ligand-dependent) and promoting (receptor processing) axon growth in developing neurons.</abstract><oa>free_for_read</oa></addata></record>
fulltext	fulltext_linktorsrc
identifier
ispartof
issn
language	eng
recordid	cdi_csuc_recercat_oai_recercat_cat_2072_505385
source	Recercat
subjects	Animals Axons Cells, Cultured Humans Mice Nonmuscle Myosin Type IIA Presenilin-1 Receptor, EphA3 Rhoa GTP-Binding Protein Signal Transduction
title	Presenilin/γ-secretase-dependent epha3 processing mediates axon elongation through non-muscle myosin IIA
url	https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T15%3A29%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-csuc_XX2&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Presenilin/%CE%B3-secretase-dependent%20epha3%20processing%20mediates%20axon%20elongation%20through%20non-muscle%20myosin%20IIA&rft.au=Javier,%20Miriam&rft.date=2019&rft_id=info:doi/&rft_dat=%3Ccsuc_XX2%3Eoai_recercat_cat_2072_505385%3C/csuc_XX2%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true