Cellular and Molecular Life Sciences

, Volume 75, Issue 22, pp 4207–4222 | Cite as

Neuronal GAP-Porf-2 transduces EphB1 signaling to brake axon growth

  • Guo-Hui Huang
  • Lin Guo
  • Liang Zhu
  • Xian-Dong Liu
  • Zhao-Liang Sun
  • Hong-Jiang Li
  • Nan-Jie XuEmail author
  • Dong-Fu FengEmail author
Original Article


Axonal outgrowth and guidance require numerous extracellular cues and intracellular mediators that transduce signals in the growth cone to regulate cytoskeletal dynamics. However, the way in which cytoskeletal effectors respond to these signals remains elusive. Here, we demonstrate that Porf-2, a neuron-expressed RhoGTPase-activating protein, plays an essential role in the inhibition of initial axon growth by restricting the expansion of the growth cone in a cell-autonomous manner. Furthermore, the EphB1 receptor is identified as an upstream controller that binds and regulates Porf-2 specifically upon extracellular ephrin-B stimulation. The activated EphB forward signal deactivates Rac1 through the GAP domain of Porf-2, which inhibits growth cone formation and brakes axon growth. Our results therefore provide a novel GAP that regulates axon growth and braking sequentially through Eph receptor-independent and Eph receptor-dependent pathways.


Axon growth Porf-2 EphB GAP Vilse 



GTPase-activating proteins


Guanine nucleotide exchange factors


Preoptic regulatory factor-2


Mass spectrometry


Wild type






Short hairpin RNA


Cyclic adenosine monophosphate




Neural stem cell




Connector enhancer of KSR-2


Green fluorescent protein


Fluorescein isothiocyanate


Bovine serum albumin


Glutathione S-transferase


p21-binding domain



We thank Prof. Jialin C. Zheng for providing the PDMS stamp model used in the stripe assay.

Author contributions

G-HH and LG designed and performed the experiments and wrote the manuscript. LZ, X-DL, Z-LS and H-JL performed the data and statistical analysis. N-JX and D-FF designed the experiments and revised the manuscript critically. All authors agree that all the questions related to the accuracy or integrity of the paper have been appropriately investigated and resolved and have given the final approval of the version to be published.


This study was supported by the National Natural Science Foundation of China (81772059 to D.-F.F, 31671062 and 31371097 to N.-J.X.), National Basic Research Program of China (Program 973 Grant 2014CB965002), 1000-Talents Program, Grants of Shanghai Brain-Intelligence Project from STCSM (16JC1420501), and the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning (No. 2013-25) to N.-J.X.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

18_2018_2858_MOESM1_ESM.docx (371 kb)
Supplementary material 1 (DOCX 371 kb)


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Guo-Hui Huang
    • 1
    • 2
    • 3
  • Lin Guo
    • 4
    • 5
  • Liang Zhu
    • 1
  • Xian-Dong Liu
    • 4
    • 5
  • Zhao-Liang Sun
    • 1
  • Hong-Jiang Li
    • 1
  • Nan-Jie Xu
    • 4
    • 5
    • 6
    Email author
  • Dong-Fu Feng
    • 1
    • 3
    Email author
  1. 1.Department of Neurosurgery, Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.Department of Neurosurgery, Shanghai Tenth People’s HospitalTongji University School of MedicineShanghaiChina
  3. 3.Institute of Traumatic MedicineShanghai Jiao Tong University School of MedicineShanghaiChina
  4. 4.Center for Brain Science Research, Department of Anatomy and PhysiologyShanghai Jiao Tong University School of MedicineShanghaiChina
  5. 5.Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and InflammationShanghai Jiao Tong University School of MedicineShanghaiChina
  6. 6.Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of EducationShanghai Jiao Tong University School of MedicineShanghaiChina

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