Wingless-type family member 3A triggers neuronal polarization via cross-activation of the insulin-like growth factor-1 receptor pathway
Initial axonal elongation is essential for neuronal polarization and requires polarized activation of IGF-1 receptors (IGF-1r) and the phosphatidylinositol 3 kinase (PI3k) pathway. Wingless-type family growth factors (Wnts) have also been implied in the regulation of axonal development. It is not kn...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-10-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fncel.2013.00194/full |
| _version_ | 1828406743774789632 |
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| author | Maria Eugenia Bernis Mariana eOksdath Sebastian eDupraz Alvaro F. Nieto Guil Marisa M. Fernandez Emilio L. Malchiodi Silvana B. Rosso Santiago eQuiroga |
| author_facet | Maria Eugenia Bernis Mariana eOksdath Sebastian eDupraz Alvaro F. Nieto Guil Marisa M. Fernandez Emilio L. Malchiodi Silvana B. Rosso Santiago eQuiroga |
| author_sort | Maria Eugenia Bernis |
| collection | DOAJ |
| description | Initial axonal elongation is essential for neuronal polarization and requires polarized activation of IGF-1 receptors (IGF-1r) and the phosphatidylinositol 3 kinase (PI3k) pathway. Wingless-type family growth factors (Wnts) have also been implied in the regulation of axonal development. It is not known, however, if Wnts have any participation in the regulation of initial axonal outgrowth and the establishment of neuronal polarity. We used cultured hippocampal neurons and growth cone particles (GCPs) isolated from fetal rat brain to show that stimulation with the wingless family factor 3A (Wnt3a) was sufficient to promote neuronal polarization in the absence of IGF-1 or high insulin. We also show that Wnt3a triggered a strong activation of IGF-1r, PI3k and Akt in developmental Stage 2 neurons and that the presence of activatable IGF-1r and PI3k activation were necessary for Wnt3a polarizing effects. Surface plasmon resonance (SPR) experiments show that Wnt3a did not bind specifically to the IGF-1r. Using crosslinking and immuno-precipitation experiments, we show that stimulation with Wnt3a triggered the formation of a complex including IGF-1r-Wnt3a-Frizzled-7. We conclude that Wnt3a triggers polarization of neurons via cross-activation of the IGF-1r/PI3k pathway upon binding to Fz7. |
| first_indexed | 2024-12-10T11:16:07Z |
| format | Article |
| id | doaj.art-52727fa87d2341baa40f6e9131879783 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-10T11:16:07Z |
| publishDate | 2013-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-52727fa87d2341baa40f6e91318797832022-12-22T01:51:10ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022013-10-01710.3389/fncel.2013.0019465106Wingless-type family member 3A triggers neuronal polarization via cross-activation of the insulin-like growth factor-1 receptor pathwayMaria Eugenia Bernis0Mariana eOksdath1Sebastian eDupraz2Alvaro F. Nieto Guil3Marisa M. Fernandez4Emilio L. Malchiodi5Silvana B. Rosso6Santiago eQuiroga7Fac. de Ciencias Químicas, Universidad Nacional de Córdoba-CONICETFac. de Ciencias Químicas, Universidad Nacional de Córdoba-CONICETFac. de Ciencias Químicas, Universidad Nacional de Córdoba-CONICETFac. de Ciencias Químicas, Universidad Nacional de Córdoba-CONICETFacultad de Farmacia y Bioquímica, UBAFacultad de Farmacia y Bioquímica, UBAFac. de Ciencias Químicas, Universidad Nacional de Córdoba-CONICETFac. de Ciencias Químicas, Universidad Nacional de Córdoba-CONICETInitial axonal elongation is essential for neuronal polarization and requires polarized activation of IGF-1 receptors (IGF-1r) and the phosphatidylinositol 3 kinase (PI3k) pathway. Wingless-type family growth factors (Wnts) have also been implied in the regulation of axonal development. It is not known, however, if Wnts have any participation in the regulation of initial axonal outgrowth and the establishment of neuronal polarity. We used cultured hippocampal neurons and growth cone particles (GCPs) isolated from fetal rat brain to show that stimulation with the wingless family factor 3A (Wnt3a) was sufficient to promote neuronal polarization in the absence of IGF-1 or high insulin. We also show that Wnt3a triggered a strong activation of IGF-1r, PI3k and Akt in developmental Stage 2 neurons and that the presence of activatable IGF-1r and PI3k activation were necessary for Wnt3a polarizing effects. Surface plasmon resonance (SPR) experiments show that Wnt3a did not bind specifically to the IGF-1r. Using crosslinking and immuno-precipitation experiments, we show that stimulation with Wnt3a triggered the formation of a complex including IGF-1r-Wnt3a-Frizzled-7. We conclude that Wnt3a triggers polarization of neurons via cross-activation of the IGF-1r/PI3k pathway upon binding to Fz7.http://journal.frontiersin.org/Journal/10.3389/fncel.2013.00194/fullneuronal polarityaxonal outgrowthWnt3aIGF-1 receptor pathwayFrizzled-7 |
| spellingShingle | Maria Eugenia Bernis Mariana eOksdath Sebastian eDupraz Alvaro F. Nieto Guil Marisa M. Fernandez Emilio L. Malchiodi Silvana B. Rosso Santiago eQuiroga Wingless-type family member 3A triggers neuronal polarization via cross-activation of the insulin-like growth factor-1 receptor pathway Frontiers in Cellular Neuroscience neuronal polarity axonal outgrowth Wnt3a IGF-1 receptor pathway Frizzled-7 |
| title | Wingless-type family member 3A triggers neuronal polarization via cross-activation of the insulin-like growth factor-1 receptor pathway |
| title_full | Wingless-type family member 3A triggers neuronal polarization via cross-activation of the insulin-like growth factor-1 receptor pathway |
| title_fullStr | Wingless-type family member 3A triggers neuronal polarization via cross-activation of the insulin-like growth factor-1 receptor pathway |
| title_full_unstemmed | Wingless-type family member 3A triggers neuronal polarization via cross-activation of the insulin-like growth factor-1 receptor pathway |
| title_short | Wingless-type family member 3A triggers neuronal polarization via cross-activation of the insulin-like growth factor-1 receptor pathway |
| title_sort | wingless type family member 3a triggers neuronal polarization via cross activation of the insulin like growth factor 1 receptor pathway |
| topic | neuronal polarity axonal outgrowth Wnt3a IGF-1 receptor pathway Frizzled-7 |
| url | http://journal.frontiersin.org/Journal/10.3389/fncel.2013.00194/full |
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