The endosomal sorting adaptor HD-PTP is required for ephrin-B:EphB signalling in cellular collapse and spinal motor axon guidance

Sci Rep. 2019 Aug 16;9(1):11945. doi: 10.1038/s41598-019-48421-9.


The signalling output of many transmembrane receptors that mediate cell-cell communication is restricted by the endosomal sorting complex required for transport (ESCRT), but the impact of this machinery on Eph tyrosine kinase receptor function is unknown. We identified the ESCRT-associated adaptor protein HD-PTP as part of an EphB2 proximity-dependent biotin identification (BioID) interactome, and confirmed this association using co-immunoprecipitation. HD-PTP loss attenuates the ephrin-B2:EphB2 signalling-induced collapse of cultured cells and axonal growth cones, and results in aberrant guidance of chick spinal motor neuron axons in vivo. HD-PTP depletion abrogates ephrin-B2-induced EphB2 clustering, and EphB2 and Src family kinase activation. HD-PTP loss also accelerates ligand-induced EphB2 degradation, contrasting the effects of HD-PTP loss on the relay of signals from other cell surface receptors. Our results link Eph function to the ESCRT machinery and demonstrate a role for HD-PTP in the earliest steps of ephrin-B:EphB signalling, as well as in obstructing premature receptor depletion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Axons / ultrastructure
  • Chick Embryo
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Endosomes / metabolism*
  • Endosomes / ultrastructure
  • Ephrin-B2 / genetics*
  • Ephrin-B2 / metabolism
  • Gene Expression Regulation
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Motor Neurons / metabolism*
  • Motor Neurons / ultrastructure
  • Primary Cell Culture
  • Protein Tyrosine Phosphatases, Non-Receptor / genetics*
  • Protein Tyrosine Phosphatases, Non-Receptor / metabolism
  • Proteolysis
  • Receptor, EphB2 / genetics*
  • Receptor, EphB2 / metabolism
  • Signal Transduction
  • Spinal Cord / metabolism
  • Spinal Cord / ultrastructure
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism


  • Endosomal Sorting Complexes Required for Transport
  • Ephrin-B2
  • Receptor, EphB2
  • src-Family Kinases
  • Protein Tyrosine Phosphatases, Non-Receptor