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

Chenying Guo, Kin Sang Cho, Yingqian Li, Kissauo Tchedre, Christian Antolik, Jie Ma, Justin Chew, Tor Paaske Utheim, Xizhong A. Huang, Honghua Yu, Muhammad Taimur A. Malik, Nada Anzak, Dong Feng Chen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number2054
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'IGFBPL1 Regulates Axon Growth through IGF-1-mediated Signaling Cascades'. Together they form a unique fingerprint.

Cite this