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The Intracellular Domain Orchestrates Notch1 Polarization and Activation by Shear Stress
The Intracellular Domain Orchestrates Notch1 Polarization and Activation by Shear Stress
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202104833
- ISBN
- 9798293856138
- DDC
- 610
- 저자명
- Singh, Tania.
- 서명/저자
- The Intracellular Domain Orchestrates Notch1 Polarization and Activation by Shear Stress
- 발행사항
- [Sl] : University of California, San Francisco, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 133 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-03, Section: B.
- 주기사항
- Includes supplementary digital materials.
- 주기사항
- Advisor: Kutys, Matthew.
- 학위논문주기
- Thesis (Ph.D.)--University of California, San Francisco, 2025.
- 초록/해제
- 요약Hemodynamic shear stress regulates endothelial phenotype through activation of Notch1 signaling, yet the mechanistic basis for this activation is unclear. Here, I establish a fluid shear stress-dependent mechanism of Notch1 activation in blood endothelia that is distinct from canonical ligand trans-endocytosis. Application of laminar flow triggers the rapid spatial polarization of full-length Notch1 heterodimers into downstream membrane microdomains. Unlike canonical transactivation, I find that this response occurs independently of ligand redistribution, and Notch1 receptors are cis-endocytosed into the receptor-bearing cell within polarized microdomains prior to proteolytic activation. Furthermore, I discover that the Notch1 intracellular domain (ICD) critically orchestrates receptor polarization and proteolytic activation in response to flow but is dispensable for canonical ligand trans-activation. Shear stress increases ICD interaction with annexin A2 and caveolar proteins which I demonstrate play critical roles in controlling Notch1 endocytosis and proteolytic compartmentalization. This thesis defines a flow-specific Notch1 mechanotransduction pathway linking receptor polarization and endocytosis with proteolytic activation and establishes new mechanisms regulating Notch receptor activation.
- 일반주제명
- Bioengineering
- 일반주제명
- Cellular biology
- 일반주제명
- Molecular biology
- 키워드
- Notch1
- 키워드
- Vasculature
- 기타저자
- University of California, San Francisco Bioengineering
- 기본자료저록
- Dissertations Abstracts International. 87-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520260202104833
■006m o d
■007cr#unu||||||||
■020 ▼a9798293856138
■035 ▼a(MiAaPQ)AAI32171005
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a610
■1001 ▼aSingh, Tania.▼0(orcid)0000-0003-0692-4821
■24510▼aThe Intracellular Domain Orchestrates Notch1 Polarization and Activation by Shear Stress
■260 ▼a[Sl]▼bUniversity of California, San Francisco▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a133 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-03, Section: B.
■500 ▼aIncludes supplementary digital materials.
■500 ▼aAdvisor: Kutys, Matthew.
■5021 ▼aThesis (Ph.D.)--University of California, San Francisco, 2025.
■520 ▼aHemodynamic shear stress regulates endothelial phenotype through activation of Notch1 signaling, yet the mechanistic basis for this activation is unclear. Here, I establish a fluid shear stress-dependent mechanism of Notch1 activation in blood endothelia that is distinct from canonical ligand trans-endocytosis. Application of laminar flow triggers the rapid spatial polarization of full-length Notch1 heterodimers into downstream membrane microdomains. Unlike canonical transactivation, I find that this response occurs independently of ligand redistribution, and Notch1 receptors are cis-endocytosed into the receptor-bearing cell within polarized microdomains prior to proteolytic activation. Furthermore, I discover that the Notch1 intracellular domain (ICD) critically orchestrates receptor polarization and proteolytic activation in response to flow but is dispensable for canonical ligand trans-activation. Shear stress increases ICD interaction with annexin A2 and caveolar proteins which I demonstrate play critical roles in controlling Notch1 endocytosis and proteolytic compartmentalization. This thesis defines a flow-specific Notch1 mechanotransduction pathway linking receptor polarization and endocytosis with proteolytic activation and establishes new mechanisms regulating Notch receptor activation.
■590 ▼aSchool code: 0034.
■650 4▼aBioengineering
■650 4▼aCellular biology
■650 4▼aMolecular biology
■653 ▼aMechanotransduction
■653 ▼aNotch1
■653 ▼aVasculature
■653 ▼aIntracellular domain
■653 ▼aHemodynamic shear stress
■690 ▼a0202
■690 ▼a0379
■690 ▼a0307
■71020▼aUniversity of California, San Francisco▼bBioengineering.
■7730 ▼tDissertations Abstracts International▼g87-03B.
■790 ▼a0034
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17359094▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
