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Structural and biochemical insights into the role of testis-expressed gene 14 (TEX14) in forming the stable intercellular bridges of germ cells

Intercellular bridges are a conserved feature of spermatogenesis in mammalian germ cells and derive from arresting cell abscission at the final stage of cytokinesis. However, it remains to be fully understood how germ cell abscission is arrested in the presence of general cytokinesis components. The... Full description

Journal Title: Proceedings of the National Academy of Sciences 06 October 2015, Vol.112(40), p.12372
Main Author: Hee Jung Kim
Other Authors: Jungbin Yoon , Atsushi Matsuura , Jung-Hyun Na , Won-Kyu Lee , Hyunook Kim , Ji Woong Choi , Ji Eun Park , Sung-Jean Park , Kyung Tae Kim , Rakwoo Chang , Byung Il Lee , Yeon Gyu Yu , Yeon-Kyun Shin , Cherlhyun Jeong , Kunsoo Rhee , Hyung Ho Lee
Format: Electronic Article Electronic Article
Language: English
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ID: ISSN: 0027-8424 ; E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1418606112
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recordid: pnas_s112_40_12372
title: Structural and biochemical insights into the role of testis-expressed gene 14 (TEX14) in forming the stable intercellular bridges of germ cells
format: Article
creator:
  • Hee Jung Kim
  • Jungbin Yoon
  • Atsushi Matsuura
  • Jung-Hyun Na
  • Won-Kyu Lee
  • Hyunook Kim
  • Ji Woong Choi
  • Ji Eun Park
  • Sung-Jean Park
  • Kyung Tae Kim
  • Rakwoo Chang
  • Byung Il Lee
  • Yeon Gyu Yu
  • Yeon-Kyun Shin
  • Cherlhyun Jeong
  • Kunsoo Rhee
  • Hyung Ho Lee
subjects:
  • Sciences (General)
ispartof: Proceedings of the National Academy of Sciences, 06 October 2015, Vol.112(40), p.12372
description: Intercellular bridges are a conserved feature of spermatogenesis in mammalian germ cells and derive from arresting cell abscission at the final stage of cytokinesis. However, it remains to be fully understood how germ cell abscission is arrested in the presence of general cytokinesis components. The TEX14 (testis-expressed gene 14) protein is recruited to the midbody and plays a key role in the inactivation of germ cell abscission. To gain insights into the structural organization of TEX14 at the midbody, we have determined the crystal structures of the EABR [endosomal sorting complex required for transport (ESCRT) and ALIX-binding region] of CEP55 bound to the TEX14 peptide (or its chimeric peptides) and performed functional characterization of the CEP55-TEX14 interaction by multiexperiment analyses. We show that TEX14 interacts with CEP55-EABR via its AxGPPx...Y (Ala793, Gly795, Pro796, Pro797, and Tyr801) and PP (Pro803 and Pro804) sequences, which together form the AxGPPx...YxPP motif. TEX14 competitively binds to CEP55-EABR to prevent the recruitment of ALIX, which is a component of the ESCRT machinery with the AxGPPx...Y motif. We also demonstrate that a high affinity and a low dissociation rate of TEX14 to CEP55, and an increase in the local concentration of TEX14, cooperatively prevent ALIX from recruiting ESCRT complexes to the midbody. The action mechanism of TEX14 suggests a scheme of how to inactivate the abscission of abnormal cells, including cancer cells. (ProQuest: ... denotes formulae/symbols omitted.)
language: eng
source:
identifier: ISSN: 0027-8424 ; E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1418606112
fulltext: fulltext_linktorsrc
issn:
  • 0027-8424
  • 00278424
  • 1091-6490
  • 10916490
url: Link


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titleStructural and biochemical insights into the role of testis-expressed gene 14 (TEX14) in forming the stable intercellular bridges of germ cells
creatorHee Jung Kim ; Jungbin Yoon ; Atsushi Matsuura ; Jung-Hyun Na ; Won-Kyu Lee ; Hyunook Kim ; Ji Woong Choi ; Ji Eun Park ; Sung-Jean Park ; Kyung Tae Kim ; Rakwoo Chang ; Byung Il Lee ; Yeon Gyu Yu ; Yeon-Kyun Shin ; Cherlhyun Jeong ; Kunsoo Rhee ; Hyung Ho Lee
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descriptionIntercellular bridges are a conserved feature of spermatogenesis in mammalian germ cells and derive from arresting cell abscission at the final stage of cytokinesis. However, it remains to be fully understood how germ cell abscission is arrested in the presence of general cytokinesis components. The TEX14 (testis-expressed gene 14) protein is recruited to the midbody and plays a key role in the inactivation of germ cell abscission. To gain insights into the structural organization of TEX14 at the midbody, we have determined the crystal structures of the EABR [endosomal sorting complex required for transport (ESCRT) and ALIX-binding region] of CEP55 bound to the TEX14 peptide (or its chimeric peptides) and performed functional characterization of the CEP55-TEX14 interaction by multiexperiment analyses. We show that TEX14 interacts with CEP55-EABR via its AxGPPx...Y (Ala793, Gly795, Pro796, Pro797, and Tyr801) and PP (Pro803 and Pro804) sequences, which together form the AxGPPx...YxPP motif. TEX14 competitively binds to CEP55-EABR to prevent the recruitment of ALIX, which is a component of the ESCRT machinery with the AxGPPx...Y motif. We also demonstrate that a high affinity and a low dissociation rate of TEX14 to CEP55, and an increase in the local concentration of TEX14, cooperatively prevent ALIX from recruiting ESCRT complexes to the midbody. The action mechanism of TEX14 suggests a scheme of how to inactivate the abscission of abnormal cells, including cancer cells. (ProQuest: ... denotes formulae/symbols omitted.)
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