IGFBPL1 Regulates Axon Growth through IGF-1-mediated Signaling Cascades

Activation of axonal growth program is a critical step in successful optic nerve regeneration following injury. Yet the molecular mechanisms that orchestrate this developmental transition are not fully understood. Here we identified a novel regulator, insulin-like growth factor binding protein-like...

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Published in:	Scientific reports Vol. 8; no. 1; pp. 2054 - 13
Main Authors:	Guo, Chenying, Cho, Kin-Sang, Li, Yingqian, Tchedre, Kissauo, Antolik, Christian, Ma, Jie, Chew, Justin, Utheim, Tor Paaske, Huang, Xizhong A., Yu, Honghua, Malik, Muhammad Taimur A., Anzak, Nada, Chen, Dong Feng
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01.02.2018 Nature Publishing Group
Subjects:	13/106 13/109 14/19 14/28 38/89 631/378/1687 631/378/2571 82/1 96/95 Animals Axonogenesis Calcium Signaling Calcium signalling Cells, Cultured Central nervous system Humanities and Social Sciences Insulin Insulin-Like Growth Factor Binding Proteins - genetics Insulin-Like Growth Factor Binding Proteins - metabolism Insulin-like growth factor I Insulin-Like Growth Factor I - metabolism Insulin-like growth factors Mice Mice, Inbred C57BL Molecular modelling multidisciplinary Neuronal Outgrowth Optic nerve PC12 Cells Phosphorylation Protein Binding Rapamycin Rats Regeneration Retina Retinal ganglion cells Retinal Ganglion Cells - cytology Retinal Ganglion Cells - metabolism Science Science (multidisciplinary) TOR protein TOR Serine-Threonine Kinases - metabolism Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism
ISSN:	2045-2322, 2045-2322
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Abstract	Activation of axonal growth program is a critical step in successful optic nerve regeneration following injury. Yet the molecular mechanisms that orchestrate this developmental transition are not fully understood. Here we identified a novel regulator, insulin-like growth factor binding protein-like 1 (IGFBPL1), for the growth of retinal ganglion cell (RGC) axons. Expression of IGFBPL1 correlates with RGC axon growth in development, and acute knockdown of IGFBPL1 with shRNA or IGFBPL1 knockout in vivo impaired RGC axon growth. In contrast, administration of IGFBPL1 promoted axon growth. Moreover, IGFBPL1 bound to insulin-like growth factor 1 (IGF-1) and subsequently induced calcium signaling and mammalian target of rapamycin (mTOR) phosphorylation to stimulate axon elongation. Blockage of IGF-1 signaling abolished IGFBPL1-mediated axon growth, and vice versa , IGF-1 required the presence of IGFBPL1 to promote RGC axon growth. These data reveal a novel element in the control of RGC axon growth and suggest an unknown signaling loop in the regulation of the pleiotropic functions of IGF-1. They suggest new therapeutic target for promoting optic nerve and axon regeneration and repair of the central nervous system.
AbstractList	Activation of axonal growth program is a critical step in successful optic nerve regeneration following injury. Yet the molecular mechanisms that orchestrate this developmental transition are not fully understood. Here we identified a novel regulator, insulin-like growth factor binding protein-like 1 (IGFBPL1), for the growth of retinal ganglion cell (RGC) axons. Expression of IGFBPL1 correlates with RGC axon growth in development, and acute knockdown of IGFBPL1 with shRNA or IGFBPL1 knockout in vivo impaired RGC axon growth. In contrast, administration of IGFBPL1 promoted axon growth. Moreover, IGFBPL1 bound to insulin-like growth factor 1 (IGF-1) and subsequently induced calcium signaling and mammalian target of rapamycin (mTOR) phosphorylation to stimulate axon elongation. Blockage of IGF-1 signaling abolished IGFBPL1-mediated axon growth, and vice versa , IGF-1 required the presence of IGFBPL1 to promote RGC axon growth. These data reveal a novel element in the control of RGC axon growth and suggest an unknown signaling loop in the regulation of the pleiotropic functions of IGF-1. They suggest new therapeutic target for promoting optic nerve and axon regeneration and repair of the central nervous system. Activation of axonal growth program is a critical step in successful optic nerve regeneration following injury. Yet the molecular mechanisms that orchestrate this developmental transition are not fully understood. Here we identified a novel regulator, insulin-like growth factor binding protein-like 1 (IGFBPL1), for the growth of retinal ganglion cell (RGC) axons. Expression of IGFBPL1 correlates with RGC axon growth in development, and acute knockdown of IGFBPL1 with shRNA or IGFBPL1 knockout in vivo impaired RGC axon growth. In contrast, administration of IGFBPL1 promoted axon growth. Moreover, IGFBPL1 bound to insulin-like growth factor 1 (IGF-1) and subsequently induced calcium signaling and mammalian target of rapamycin (mTOR) phosphorylation to stimulate axon elongation. Blockage of IGF-1 signaling abolished IGFBPL1-mediated axon growth, and vice versa, IGF-1 required the presence of IGFBPL1 to promote RGC axon growth. These data reveal a novel element in the control of RGC axon growth and suggest an unknown signaling loop in the regulation of the pleiotropic functions of IGF-1. They suggest new therapeutic target for promoting optic nerve and axon regeneration and repair of the central nervous system.Activation of axonal growth program is a critical step in successful optic nerve regeneration following injury. Yet the molecular mechanisms that orchestrate this developmental transition are not fully understood. Here we identified a novel regulator, insulin-like growth factor binding protein-like 1 (IGFBPL1), for the growth of retinal ganglion cell (RGC) axons. Expression of IGFBPL1 correlates with RGC axon growth in development, and acute knockdown of IGFBPL1 with shRNA or IGFBPL1 knockout in vivo impaired RGC axon growth. In contrast, administration of IGFBPL1 promoted axon growth. Moreover, IGFBPL1 bound to insulin-like growth factor 1 (IGF-1) and subsequently induced calcium signaling and mammalian target of rapamycin (mTOR) phosphorylation to stimulate axon elongation. Blockage of IGF-1 signaling abolished IGFBPL1-mediated axon growth, and vice versa, IGF-1 required the presence of IGFBPL1 to promote RGC axon growth. These data reveal a novel element in the control of RGC axon growth and suggest an unknown signaling loop in the regulation of the pleiotropic functions of IGF-1. They suggest new therapeutic target for promoting optic nerve and axon regeneration and repair of the central nervous system. Activation of axonal growth program is a critical step in successful optic nerve regeneration following injury. Yet the molecular mechanisms that orchestrate this developmental transition are not fully understood. Here we identified a novel regulator, insulin-like growth factor binding protein-like 1 (IGFBPL1), for the growth of retinal ganglion cell (RGC) axons. Expression of IGFBPL1 correlates with RGC axon growth in development, and acute knockdown of IGFBPL1 with shRNA or IGFBPL1 knockout in vivo impaired RGC axon growth. In contrast, administration of IGFBPL1 promoted axon growth. Moreover, IGFBPL1 bound to insulin-like growth factor 1 (IGF-1) and subsequently induced calcium signaling and mammalian target of rapamycin (mTOR) phosphorylation to stimulate axon elongation. Blockage of IGF-1 signaling abolished IGFBPL1-mediated axon growth, and vice versa, IGF-1 required the presence of IGFBPL1 to promote RGC axon growth. These data reveal a novel element in the control of RGC axon growth and suggest an unknown signaling loop in the regulation of the pleiotropic functions of IGF-1. They suggest new therapeutic target for promoting optic nerve and axon regeneration and repair of the central nervous system.
ArticleNumber	2054
Author	Yu, Honghua Huang, Xizhong A. Chew, Justin Cho, Kin-Sang Utheim, Tor Paaske Malik, Muhammad Taimur A. Antolik, Christian Tchedre, Kissauo Guo, Chenying Li, Yingqian Anzak, Nada Chen, Dong Feng Ma, Jie
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Snippet	Activation of axonal growth program is a critical step in successful optic nerve regeneration following injury. Yet the molecular mechanisms that orchestrate...
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SubjectTerms	13/106 13/109 14/19 14/28 38/89 631/378/1687 631/378/2571 82/1 96/95 Animals Axonogenesis Calcium Signaling Calcium signalling Cells, Cultured Central nervous system Humanities and Social Sciences Insulin Insulin-Like Growth Factor Binding Proteins - genetics Insulin-Like Growth Factor Binding Proteins - metabolism Insulin-like growth factor I Insulin-Like Growth Factor I - metabolism Insulin-like growth factors Mice Mice, Inbred C57BL Molecular modelling multidisciplinary Neuronal Outgrowth Optic nerve PC12 Cells Phosphorylation Protein Binding Rapamycin Rats Regeneration Retina Retinal ganglion cells Retinal Ganglion Cells - cytology Retinal Ganglion Cells - metabolism Science Science (multidisciplinary) TOR protein TOR Serine-Threonine Kinases - metabolism Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism
Title	IGFBPL1 Regulates Axon Growth through IGF-1-mediated Signaling Cascades
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