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

Sylvie Lahaie; Daniel Morales; Halil Bagci; Noumeira Hamoud; Charles Etienne Castonguay; Jalal M. Kazan; Guillaume Desrochers; Avihu Klar; Anne Claude Gingras; Arnim Pause; Jean François Côté; Artur Kania

doi:10.1038/s41598-019-48421-9

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

Sylvie Lahaie, Daniel Morales, Halil Bagci, Noumeira Hamoud, Charles Etienne Castonguay, Jalal M. Kazan, Guillaume Desrochers, Avihu Klar, Anne Claude Gingras, Arnim Pause, Jean François Côté, Artur Kania^*

^*Corresponding author for this work

Department of Medical Neurobiology

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

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.

Original language	American English
Article number	11945
Journal	Scientific Reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-48421-9
State	Published - 1 Dec 2019

Bibliographical note

Funding Information:
The authors thank E. Olafson, J. Cardin and M. Liang for technical assistance, L. Delorme for secretarial assistance, and N. Bisson for critical comments on an earlier version of the manuscript. D.M. was a recipient of a Mexican National Council for Science and Technology (CONACYT) international PhD scholarship, received funding from the McGill University Integrated Program in Neuroscience, and is currently funded by a Swiss Government Excellence Postdoctoral Scholarship (#2018.0483). H.B. was supported by a doctoral training award from the Fonds de recherché du Québec – Santé (FRQS) (#33603). G.D. was supported by a postdoctoral training award from the FRQS. This work was supported by grants from the Canadian Institutes of Health Research (PJT-152966 to A.P, MOP-97758 and MOP-77556 to A. Kania), the Canadian Cancer Society Research Institute (705376 to A.P.), NSERC (RGPIN-2016-04808 to J.F.C.), and Brain Canada, Canadian Foundation for Innovation, and the W. Garfield Weston Foundation to A. Kania. J.F.C. holds the TRANSAT chair in breast cancer research. A. Kania and J.F.C. were also supported by FRSQ Chercheur-boursier Senior career awards.

Publisher Copyright:
© 2019, The Author(s).

Access to Document

10.1038/s41598-019-48421-9

Cite this

Lahaie, S., Morales, D., Bagci, H., Hamoud, N., Castonguay, C. E., Kazan, J. M., Desrochers, G., Klar, A., Gingras, A. C., Pause, A., Côté, J. F., & Kania, A. (2019). The endosomal sorting adaptor HD-PTP is required for ephrin-B:EphB signalling in cellular collapse and spinal motor axon guidance. Scientific Reports, 9(1), Article 11945. https://doi.org/10.1038/s41598-019-48421-9

@article{4f66dec1610f4b049d4d6b48497b8fb1,

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

abstract = "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.",

author = "Sylvie Lahaie and Daniel Morales and Halil Bagci and Noumeira Hamoud and Castonguay, {Charles Etienne} and Kazan, {Jalal M.} and Guillaume Desrochers and Avihu Klar and Gingras, {Anne Claude} and Arnim Pause and C{\^o}t{\'e}, {Jean Fran{\c c}ois} and Artur Kania",

note = "Funding Information: The authors thank E. Olafson, J. Cardin and M. Liang for technical assistance, L. Delorme for secretarial assistance, and N. Bisson for critical comments on an earlier version of the manuscript. D.M. was a recipient of a Mexican National Council for Science and Technology (CONACYT) international PhD scholarship, received funding from the McGill University Integrated Program in Neuroscience, and is currently funded by a Swiss Government Excellence Postdoctoral Scholarship (#2018.0483). H.B. was supported by a doctoral training award from the Fonds de recherch{\'e} du Qu{\'e}bec – Sant{\'e} (FRQS) (#33603). G.D. was supported by a postdoctoral training award from the FRQS. This work was supported by grants from the Canadian Institutes of Health Research (PJT-152966 to A.P, MOP-97758 and MOP-77556 to A. Kania), the Canadian Cancer Society Research Institute (705376 to A.P.), NSERC (RGPIN-2016-04808 to J.F.C.), and Brain Canada, Canadian Foundation for Innovation, and the W. Garfield Weston Foundation to A. Kania. J.F.C. holds the TRANSAT chair in breast cancer research. A. Kania and J.F.C. were also supported by FRSQ Chercheur-boursier Senior career awards. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41598-019-48421-9",

language = "American English",

volume = "9",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - The endosomal sorting adaptor HD-PTP is required for ephrin-B:EphB signalling in cellular collapse and spinal motor axon guidance

AU - Lahaie, Sylvie

AU - Morales, Daniel

AU - Bagci, Halil

AU - Hamoud, Noumeira

AU - Castonguay, Charles Etienne

AU - Kazan, Jalal M.

AU - Desrochers, Guillaume

AU - Klar, Avihu

AU - Gingras, Anne Claude

AU - Pause, Arnim

AU - Côté, Jean François

AU - Kania, Artur

N1 - Funding Information: The authors thank E. Olafson, J. Cardin and M. Liang for technical assistance, L. Delorme for secretarial assistance, and N. Bisson for critical comments on an earlier version of the manuscript. D.M. was a recipient of a Mexican National Council for Science and Technology (CONACYT) international PhD scholarship, received funding from the McGill University Integrated Program in Neuroscience, and is currently funded by a Swiss Government Excellence Postdoctoral Scholarship (#2018.0483). H.B. was supported by a doctoral training award from the Fonds de recherché du Québec – Santé (FRQS) (#33603). G.D. was supported by a postdoctoral training award from the FRQS. This work was supported by grants from the Canadian Institutes of Health Research (PJT-152966 to A.P, MOP-97758 and MOP-77556 to A. Kania), the Canadian Cancer Society Research Institute (705376 to A.P.), NSERC (RGPIN-2016-04808 to J.F.C.), and Brain Canada, Canadian Foundation for Innovation, and the W. Garfield Weston Foundation to A. Kania. J.F.C. holds the TRANSAT chair in breast cancer research. A. Kania and J.F.C. were also supported by FRSQ Chercheur-boursier Senior career awards. Publisher Copyright: © 2019, The Author(s).

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85070996087&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-48421-9

DO - 10.1038/s41598-019-48421-9

M3 - Article

C2 - 31420572

AN - SCOPUS:85070996087

SN - 2045-2322

VL - 9

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 11945

ER -

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

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this