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Molecular Mechanisms of Exosome Secretion
Molecular Mechanisms of Exosome Secretion
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211150949
- ISBN
- 9798382831008
- DDC
- 574
- 저자명
- Liu, Di-Ao.
- 서명/저자
- Molecular Mechanisms of Exosome Secretion
- 발행사항
- [Sl] : University of Pennsylvania, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 190 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- 주기사항
- Advisor: Guo, Wei;Gallagher, Kimberly.
- 학위논문주기
- Thesis (Ph.D.)--University of Pennsylvania, 2024.
- 초록/해제
- 요약Exosomes are small (30-150 nm) extracellular vesicles (EVs) that obtain their membrane through the inward invagination of the endosomes, which are known as multivesicular endosomes (MVEs). Exosomes are secreted to the extracellular milieu when MVEs dock and fuse with the plasma membrane. However, MVEs can also fuse with lysosomes for degradation. How MVEs are directed to the plasma membrane rather than to lysosomes is unclear. My thesis work mainly focused on the molecular mechanisms that control the exocytic trafficking of MVEs and, ultimately, exosome secretion. We found that the conversion of phosphatidylinositol-3-phosphate (PI(3)P) to phosphatidylinositol-4-phosphate (PI(4)P) catalyzed by Myotubularin 1 (MTM1) and phosphatidylinositol 4-kinase type IIα (PI4KIIα) on the surface of MVEs mediates the recruitment of the exocyst complex. The exocyst then targets the MVEs to the plasma membrane for exosome secretion. Disrupting PI(4)P generation or exocyst function blocked exosomal secretion of Programmed death-ligand 1 (PD-L1), a key immune checkpoint protein in tumor cells, and led to its accumulation in lysosomes.In collaboration with the lab members, we also found that cells respond to extracellular matrix (ECM) stiffness for exosome secretion. Increased ECM stiffness activates Akt, which directly phosphorylates Rabin8 and promotes its guanine nucleotide exchange activity toward Rab8 for the exocytic trafficking of MVEs and exosome secretion. Together, my work suggests that exocytic trafficking of MVEs and exosome secretion is mediated by phospholipids, Rab GTPases, and the exocyst complex, which is regulated by signaling molecules in response to extracellular cues.
- 일반주제명
- Biology
- 일반주제명
- Cellular biology
- 일반주제명
- Molecular biology
- 일반주제명
- Immunology
- 키워드
- Tumor cells
- 기타저자
- University of Pennsylvania Biology
- 기본자료저록
- Dissertations Abstracts International. 85-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■007cr#unu||||||||
■020 ▼a9798382831008
■035 ▼a(MiAaPQ)AAI30992944
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aLiu, Di-Ao.
■24510▼aMolecular Mechanisms of Exosome Secretion
■260 ▼a[Sl]▼bUniversity of Pennsylvania▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a190 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-12, Section: B.
■500 ▼aAdvisor: Guo, Wei;Gallagher, Kimberly.
■5021 ▼aThesis (Ph.D.)--University of Pennsylvania, 2024.
■520 ▼aExosomes are small (30-150 nm) extracellular vesicles (EVs) that obtain their membrane through the inward invagination of the endosomes, which are known as multivesicular endosomes (MVEs). Exosomes are secreted to the extracellular milieu when MVEs dock and fuse with the plasma membrane. However, MVEs can also fuse with lysosomes for degradation. How MVEs are directed to the plasma membrane rather than to lysosomes is unclear. My thesis work mainly focused on the molecular mechanisms that control the exocytic trafficking of MVEs and, ultimately, exosome secretion. We found that the conversion of phosphatidylinositol-3-phosphate (PI(3)P) to phosphatidylinositol-4-phosphate (PI(4)P) catalyzed by Myotubularin 1 (MTM1) and phosphatidylinositol 4-kinase type IIα (PI4KIIα) on the surface of MVEs mediates the recruitment of the exocyst complex. The exocyst then targets the MVEs to the plasma membrane for exosome secretion. Disrupting PI(4)P generation or exocyst function blocked exosomal secretion of Programmed death-ligand 1 (PD-L1), a key immune checkpoint protein in tumor cells, and led to its accumulation in lysosomes.In collaboration with the lab members, we also found that cells respond to extracellular matrix (ECM) stiffness for exosome secretion. Increased ECM stiffness activates Akt, which directly phosphorylates Rabin8 and promotes its guanine nucleotide exchange activity toward Rab8 for the exocytic trafficking of MVEs and exosome secretion. Together, my work suggests that exocytic trafficking of MVEs and exosome secretion is mediated by phospholipids, Rab GTPases, and the exocyst complex, which is regulated by signaling molecules in response to extracellular cues.
■590 ▼aSchool code: 0175.
■650 4▼aBiology
■650 4▼aCellular biology
■650 4▼aMolecular biology
■650 4▼aImmunology
■653 ▼aExtracellular vesicles
■653 ▼aMultivesicular endosomes
■653 ▼aTumor cells
■653 ▼aExtracellular matrix
■690 ▼a0306
■690 ▼a0379
■690 ▼a0982
■690 ▼a0307
■71020▼aUniversity of Pennsylvania▼bBiology.
■7730 ▼tDissertations Abstracts International▼g85-12B.
■790 ▼a0175
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160284▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
