PtdIns(4,5)P2 and PtdIns(3,4)P2/PtdIns(3,4,5)P3 differentially regulate ZFYVE27 dynamics on neurite outgrowth through the FYVE domain = FYVE 도메인과 PtdIns(4,5)P2와 PtdIns(3,4)P2/PtdIns(3,4,5)P3의 상호 작용을 통한 ZFYVE27의 뉴라이트 생성 유도 조절

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Phosphatidylinositol-(4,5)-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol-(3,4,5)-triphosphate (PtdIns(3,4,5)P3) in the plasma membrane (PM) play a key role in the regulation of various cellular processes including proliferation, differentiation and survival. Their main role is to recruit a variety of signaling proteins to the PM via direct interaction with specific lipid binding domains (LBDs) and motifs in the proteins. In this study, I examined the subcellular localization of 94 distinct LBDs in order to better understand how PtdIns(4,5)P2 and/or PtdIns(3,4,5)P3 target different proteins to the PM and control their function. Surprisingly, I found that the FYVE domain of ZFYVE27 localizes to the PM. Surface plasmon resonance analysis shows that unlike canonical FYVE domains that specifically bind to phosphatidylinositol-3-phosphate this FYVE domain preferentially interacts with PtdIns(4,5)P2, PtdIns(3,4)P2 and PtdIns(3,4,5)P3 using basic amino acids inside the lipid-binding pocket. Furthermore, I found that PtdIns(4,5)P2 and PtdIns(3,4)P2/PtdIns(3,4,5)P3 differentially regulate ZFYVE27 shuttling from ER to PM via the FYVE domain. ZFYVE27 mutants with reduced affinity for PtdIns(4,5)P2, PtdIns(3,4)P2 and PtdIns(3,4,5)P3 failed to target the PM in NIH3T3 cells and promote neurite outgrowth in primary cultured hippocampal neurons. These results suggest that the novel PtdIns(4,5)P2 and PtdIns(3,4)P2/PtdIns(3,4,5)P3 selectivity of the FYVE domain of ZFYVE27 is critical for the role of ZFYVE27 in mediating neurite outgrowth.
Advisors
Heo, Won-Doresearcher허원도
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2012
Identifier
511415/325007  / 020095013
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2012.8, [ vi, 89 p. ]

Keywords

lipid binding domain; PIP3; PIP2; FYVE domain; ZFYVE27; PIP2; PIP3; lipid binding 도메인; FYVE 도메인; ZFYVE27; 뉴라이트 생성 유도; neurite outgrowth

URI
http://hdl.handle.net/10203/179822
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=511415&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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