Neuropilin-1 is a glial cell line-derived neurotrophic factor receptor in glioblastoma

Oncotarget
Shen SunDian-Shuai Gao

Abstract

The aim of this study was to identify the receptor for glial cell line-derived neurotrophic factor (GDNF) in glioblastoma multiforme (GBM). After GST pull-down assays, membrane proteins purified from C6 rat glioma cells were subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS). The differentially expressed proteins were annotated using Gene Ontology, and neuropilin-1 (NRP1) was identified as the putative GDNF receptor in glioma. NRP1 was more highly expressed in human GBM brains and C6 rat glioma cells than in normal human brains or primary rat astrocytes. Immunofluorescence staining showed that NRP1 was recruited to the membrane by GDNF, and NRP1 co-immunoprecipitated with GDNF. Using the NRP1 and GDNF protein structures to assess molecular docking in the ZDOCK server and visualization with the PyMOL Molecular Graphics System revealed 8 H-bonds and stable positive and negative electrostatic interactions between NRP1 and GDNF. RNAi knockdown of NRP1 reduced proliferation of C6 glioma cells when stimulated with GDNF. NRP1 was an independent risk factor for both survival and recurrence in GBM patients. High NRP1 mRNA expression correlated with shorter OS and DFS (OS: χ(2)=4.6720, P=0.0307; DFS: χ(2)=11.013, P=0....Continue Reading

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Citations

Apr 13, 2018·Biomedicines·Jing Hao, Jennifer S Yu
Sep 25, 2019·International Journal of Molecular Sciences·Didem Ag SeleciGeorg Garnweitner
Feb 14, 2020·Cell Communication and Signaling : CCS·Abiola Abdulrahman AyanlajaDianshuai Gao
Nov 24, 2020·International Journal of Nanomedicine·Mickaël GriesMuriel Barberi-Heyob

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Methods Mentioned

BETA
pull-down
flow cytometry
pull down
Co-IP
FACS
Immunoprecipitation
Assay
electron microscopy
X-ray
PCR

Software Mentioned

PyMOL
ZDOCK Server
PyMOL Molecular Graphics System
RNA Seq V2 RSEM
Block
PANTHER Classification System
Normal Analysis
SPSS
Modfit
PDB2PQR

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