생명과학회지 (Journal of Life Science)

  • 제22권12호
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  • Pages.1608-1613
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  • 2012
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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APP tail 1 (PAT1)과 kinesin light chains (KLCs)의 tetratricopeptide repeat (TPR) domain을 통한 결합

APP Tail 1 (PAT1) Interacts with Kinesin Light Chains (KLCs) through the Tetratricopeptide Repeat (TPR) Domain

  • 장원희 (인제대학교 의과대학 생화학교실) ;
  • 김상진 (인제대학교 의과대학 신경과학교실) ;
  • 정영주 (인제대학교 의과대학 생화학교실) ;
  • 전희재 (인제대학교 의과대학 흉부외과학교실) ;
  • 문일수 (동국대학교 의과대학 해부학교실) ;
  • 석대현 (인제대학교 의과대학 생화학교실)
  • Jang, Won Hee (Department of Biochemistry, College of Medicine, Inje University) ;
  • Kim, Sang-Jin (Department of Neurology, College of Medicine, Inje University) ;
  • Jeong, Young Joo (Department of Biochemistry, College of Medicine, Inje University) ;
  • Jun, Hee Jae (Department of Thoracic & Cardiovascular Surgery, College of Medicine, Inje University) ;
  • Moon, Il Soo (Department of Anatomy & Dongguk Medical Institute, College of Medicine, Dongguk University) ;
  • Seog, Dae-Hyun (Department of Biochemistry, College of Medicine, Inje University)
  • 투고 : 2012.11.06
  • 심사 : 2012.11.21
  • 발행 : 2012.12.30
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초록

KIF5/Kinesin-I는 경쇄(light chain)를 통하여 결합함으로써 다양한 운반체들을 미세소관을 따라 운반한다. Kinesin light chains (KLCs)은 tetratricopeptide repeat (TPR) 영역을 매개로 운반체와 결합한다. 현재까지 KLCs와 결합하는 많은 운반체들이 확인되었으나 KLCs가 어떻게 특정운반체를 인식하여 결합하는지는 아직 확실히 밝혀지지 않았다. 본 연구에서 KLC1의 TPR 영역과 결합하는 단백질을 분리하기 위하여 효모 two-hybrid system을 이용하여 탐색한 결과 amyloid precursor protein (APP)과 결합하는 것으로 보고된 protein interacting with APP tail 1 (PAT1)을 분리하였다. KLC1은 PAT1의 C-말단 부위와 결합하며, PAT1은 KLC1의 TPR 영역을 포함한 부위와 결합함을 효모 two-hybrid assay로 확인하였다. 또한 PAT1는 KLC2와도 결합하였지만 kinesin heavy chains (KHCs)인 KIF5A, KIF5B, KIF5C와는 결합하지 않았다. 단백질간 결합은 glutathione S-transferase (GST) pull-down assay와 공동면역침강으로도 확인하였다. 생쥐의 뇌 파쇄액을 PAT1 항체와 APP 항체로 면역침강을 행한 결과 KLC와 KHCs가 같이 침강하였다. 이러한 결과들은 PAT1이 Kinesin-I와 APP 포함 소포간의 상호작용을 매개한다는 것을 시사한다.

A conventional kinesin, KIF5/Kinesin-I, transports various cargoes along the microtubule through interaction between its light chain subunit and the cargoes. Kinesin light chains (KLCs) interact with many different cargoes using their tetratricopeptide repeat (TPR) domain, but the mechanism underlying recognition and binding of a specific cargo has not yet been completely elucidated. We used the yeast two-hybrid assay to identify proteins that interact with the TPR domain of KLC1. We found an interaction between the TPR domain of KLC1 and an amyloid precursor protein (APP)-binding protein PAT1 (protein interacting with APP tail 1). The yeast two-hybrid assay demonstrated that the TPR domain-containing region of KLC1 mediated binding to the C-terminal tail region of PAT1. PAT1 also bound to KLC2 but not to kinesin heavy chains (KIF5A, KIF5B, and KIF5C) in the yeast two-hybrid assay. These protein-protein interactions were also observed in the glutathione S-transferase (GST) pull-down assay and by co-immunoprecipitation. Anti-PAT1 antibody as well as anti-APP anti-body co-immunoprecipitated KLC and KHCs associated with PAT1 from mouse brain extracts. These results suggest that PAT1 could mediate interactions between Kinesin-I and APP containing vesicles.

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피인용 문헌

  1. Ferritin, an Iron Storage Protein, Associates with Kinesin 1 through the Cargo-binding Region of Kinesin Heavy Chains (KHCs) vol.26, pp.6, 2016, https://doi.org/10.5352/JLS.2016.26.6.698
  2. The Scaffolding Protein WAVE1 Associates with Kinesin 1 through the Tetratricopeptide Repeat (TPR) Domain of the Kinesin Light Chain (KLC) vol.26, pp.8, 2016, https://doi.org/10.5352/JLS.2016.26.8.963