Recruitment of UBPY and ESCRT exchange drive HD-PTP-dependent sorting of EGFR to the MVB.Citation formats

  • External authors:
  • Nazim Ali
  • Ling Zhang
  • Sandra Taylor
  • Sylvie Urbé

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Recruitment of UBPY and ESCRT exchange drive HD-PTP-dependent sorting of EGFR to the MVB. / Ali, Nazim; Zhang, Ling; Taylor, Sandra; Mironov, Alex; Urbé, Sylvie; Woodman, Philip.

In: Current biology , Vol. 23, No. 6, 18.03.2013, p. 453-461.

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Ali, Nazim ; Zhang, Ling ; Taylor, Sandra ; Mironov, Alex ; Urbé, Sylvie ; Woodman, Philip. / Recruitment of UBPY and ESCRT exchange drive HD-PTP-dependent sorting of EGFR to the MVB. In: Current biology . 2013 ; Vol. 23, No. 6. pp. 453-461.

Bibtex

@article{b44aec61f49e40c0913c078c055fe0d2,
title = "Recruitment of UBPY and ESCRT exchange drive HD-PTP-dependent sorting of EGFR to the MVB.",
abstract = "BACKGROUND: Sorting ubiquitinated epidermal growth factor receptor (EGFR) to the intralumenal vesicles of the multivesicular body requires the coordinated action of several ESCRT complexes. A central question is how EGFR transits vectorially from early, ubiquitin-binding ESCRTs to the final complex, ESCRT-III, such that cargo sequestration is coupled with intralumenal vesicle formation. RESULTS: We show that the ESCRT accessory protein HD-PTP/PTPN23 associates with EGFR and combines with the deubiquitinating enzyme UBPY/USP8 to transfer EGFR from ESCRT-0 to ESCRT-III and drive EGFR sorting to intralumenal vesicles. HD-PTP binds ESCRT-0 via two interactions with the STAM2 subunit. First, the HD-PTP Bro1 domain binds the core domain of STAM2. This is competed by the ESCRT-III subunit CHMP4B, which binds an overlapping site on HD-PTP Bro1. Second, a proline-rich peptide in HD-PTP binds the SH3 domain of STAM2. Similar proline-rich peptides on UBPY also bind STAM2 SH3 to facilitate EGFR deubiquitination. Hence, locally recruited UBPY would be expected to compete with HD-PTP for STAM2 binding at this second site. Indeed, we show that HD-PTP recruits UBPY to EGFR. Association of UBPY with HD-PTP involves UBPY interacting with HD-PTP-bound CHMP4B, as well as additional interaction(s) between UBPY and HD-PTP. CONCLUSIONS: This study identifies HD-PTP as a central coordinator of the ESCRT pathway for EGFR. Based on these studies, we propose a model whereby the concerted recruitment of CHMP4B and UBPY to HD-PTP and the engagement of UBPY by STAM2 displaces ESCRT-0 from HD-PTP, deubiquitinates EGFR, and releases ESCRT-0 from cargo in favor of ESCRT-III.",
author = "Nazim Ali and Ling Zhang and Sandra Taylor and Alex Mironov and Sylvie Urb{\'e} and Philip Woodman",
note = "BB/I012109/1, Biotechnology and Biological Sciences Research Council, United KingdomG0701140, Medical Research Council, United KingdomG0701141 and, Medical Research Council, United KingdomG0900930, Medical Research Council, United Kingdom",
year = "2013",
month = mar,
day = "18",
doi = "10.1016/j.cub.2013.02.033",
language = "English",
volume = "23",
pages = "453--461",
journal = "Current biology ",
issn = "0960-9822",
publisher = "Cell Press",
number = "6",

}

RIS

TY - JOUR

T1 - Recruitment of UBPY and ESCRT exchange drive HD-PTP-dependent sorting of EGFR to the MVB.

AU - Ali, Nazim

AU - Zhang, Ling

AU - Taylor, Sandra

AU - Mironov, Alex

AU - Urbé, Sylvie

AU - Woodman, Philip

N1 - BB/I012109/1, Biotechnology and Biological Sciences Research Council, United KingdomG0701140, Medical Research Council, United KingdomG0701141 and, Medical Research Council, United KingdomG0900930, Medical Research Council, United Kingdom

PY - 2013/3/18

Y1 - 2013/3/18

N2 - BACKGROUND: Sorting ubiquitinated epidermal growth factor receptor (EGFR) to the intralumenal vesicles of the multivesicular body requires the coordinated action of several ESCRT complexes. A central question is how EGFR transits vectorially from early, ubiquitin-binding ESCRTs to the final complex, ESCRT-III, such that cargo sequestration is coupled with intralumenal vesicle formation. RESULTS: We show that the ESCRT accessory protein HD-PTP/PTPN23 associates with EGFR and combines with the deubiquitinating enzyme UBPY/USP8 to transfer EGFR from ESCRT-0 to ESCRT-III and drive EGFR sorting to intralumenal vesicles. HD-PTP binds ESCRT-0 via two interactions with the STAM2 subunit. First, the HD-PTP Bro1 domain binds the core domain of STAM2. This is competed by the ESCRT-III subunit CHMP4B, which binds an overlapping site on HD-PTP Bro1. Second, a proline-rich peptide in HD-PTP binds the SH3 domain of STAM2. Similar proline-rich peptides on UBPY also bind STAM2 SH3 to facilitate EGFR deubiquitination. Hence, locally recruited UBPY would be expected to compete with HD-PTP for STAM2 binding at this second site. Indeed, we show that HD-PTP recruits UBPY to EGFR. Association of UBPY with HD-PTP involves UBPY interacting with HD-PTP-bound CHMP4B, as well as additional interaction(s) between UBPY and HD-PTP. CONCLUSIONS: This study identifies HD-PTP as a central coordinator of the ESCRT pathway for EGFR. Based on these studies, we propose a model whereby the concerted recruitment of CHMP4B and UBPY to HD-PTP and the engagement of UBPY by STAM2 displaces ESCRT-0 from HD-PTP, deubiquitinates EGFR, and releases ESCRT-0 from cargo in favor of ESCRT-III.

AB - BACKGROUND: Sorting ubiquitinated epidermal growth factor receptor (EGFR) to the intralumenal vesicles of the multivesicular body requires the coordinated action of several ESCRT complexes. A central question is how EGFR transits vectorially from early, ubiquitin-binding ESCRTs to the final complex, ESCRT-III, such that cargo sequestration is coupled with intralumenal vesicle formation. RESULTS: We show that the ESCRT accessory protein HD-PTP/PTPN23 associates with EGFR and combines with the deubiquitinating enzyme UBPY/USP8 to transfer EGFR from ESCRT-0 to ESCRT-III and drive EGFR sorting to intralumenal vesicles. HD-PTP binds ESCRT-0 via two interactions with the STAM2 subunit. First, the HD-PTP Bro1 domain binds the core domain of STAM2. This is competed by the ESCRT-III subunit CHMP4B, which binds an overlapping site on HD-PTP Bro1. Second, a proline-rich peptide in HD-PTP binds the SH3 domain of STAM2. Similar proline-rich peptides on UBPY also bind STAM2 SH3 to facilitate EGFR deubiquitination. Hence, locally recruited UBPY would be expected to compete with HD-PTP for STAM2 binding at this second site. Indeed, we show that HD-PTP recruits UBPY to EGFR. Association of UBPY with HD-PTP involves UBPY interacting with HD-PTP-bound CHMP4B, as well as additional interaction(s) between UBPY and HD-PTP. CONCLUSIONS: This study identifies HD-PTP as a central coordinator of the ESCRT pathway for EGFR. Based on these studies, we propose a model whereby the concerted recruitment of CHMP4B and UBPY to HD-PTP and the engagement of UBPY by STAM2 displaces ESCRT-0 from HD-PTP, deubiquitinates EGFR, and releases ESCRT-0 from cargo in favor of ESCRT-III.

U2 - 10.1016/j.cub.2013.02.033

DO - 10.1016/j.cub.2013.02.033

M3 - Article

C2 - 23477725

VL - 23

SP - 453

EP - 461

JO - Current biology

JF - Current biology

SN - 0960-9822

IS - 6

ER -