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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Vydáno v:Scientific reports Ročník 8; číslo 1; s. 2054 - 13
Hlavní autoři: 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
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 01.02.2018
Nature Publishing Group
Témata:
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631/378/1687
631/378/2571
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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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Shrnutí: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.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-20463-5