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Localization of G Protein Coupled Receptors to Primary Cilia and Its Impact on Neuronal Function
Localization of G Protein Coupled Receptors to Primary Cilia and Its Impact on Neuronal Function
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202105708
- ISBN
- 9798270223151
- DDC
- 616
- 서명/저자
- Localization of G Protein Coupled Receptors to Primary Cilia and Its Impact on Neuronal Function
- 발행사항
- [Sl] : The Ohio State University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 156 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-06, Section: B.
- 주기사항
- Advisor: Mykytyn, Kirk.
- 학위논문주기
- Thesis (Ph.D.)--The Ohio State University, 2024.
- 초록/해제
- 요약The primary cilium, a microtubule-based organelle extending from the cell body, has emerged as a pivotal player in cellular homeostasis and disease pathology. Dysfunction in proteins associated with ciliary function leads to ciliopathies, a group of disorders affecting multiple organ systems, including the central nervous system (CNS). Despite the well-established roles of primary cilia in sensory functions, their significance in neuronal processes remains incompletely understood. This dissertation investigates the localization and function of G protein-coupled receptors (GPCRs) within primary cilia, particularly focusing on the dopamine receptor 1 (D1) and its implications for neuronal signaling and behavior.Chapter 2 introduces a novel constitutive Bardet-Biedl Syndrome (BBS) mouse model, to explore the impact of BBSome dysfunction on GPCR ciliary localization. Our findings reveal disrupted localization of select GPCRs in response to BBSome loss, emphasizing the crucial role of BBS proteins in establishing ciliary GPCR pathways.Chapter 3 examines the consequences of disrupting D1 ciliary localization in D1- expressing neurons. Employing loss of Bbs1 or cilia, we observe obesity associated with reduced locomotor activity, indicating diminished D1 signaling in the CNS and underscoring the importance of neuronal cilia in GPCR signaling regulation.Chapter 4 presents transcriptomic data of the D1Bbs1+/- and D1Cilia+/- mouse lines, revealing that the loss of Bbs1 or the loss of cilia on D1-expression neurons leads to changes in gene expression. We validate a novel transgenic mouse model to resolve the D1 protein association network. In this D1-APEX2 mouse model, the localization, activation, and signaling of D1-APEX2 is equivalent to wildtype D1. Proximity labeling of Bbs4+/+ and Bbs4-/- striatal lysates reveals that the loss of Bbs4 impacts D1 protein associations.Chapter 5 presents proteomics data using proximity labeling in a D1-APEX2 mouse model to examine the D1 protein association network. Through proximity labeling, we identify known interactors of the D1 receptors and proteins involved in canonical and noncanonical signaling pathways, suggesting the existence of a signaling hub for D1.Overall, this work advances our understanding of cilia biology and GPCR signaling, shedding light on the role of primary cilia in neuronal function and its implications for disease pathology.
- 일반주제명
- Neurosciences
- 일반주제명
- Cellular biology
- 일반주제명
- Pathology
- 일반주제명
- Molecular biology
- 키워드
- Dopamine
- 키워드
- Primary cilia
- 기타저자
- The Ohio State University Neuroscience Graduate Studies Program
- 기본자료저록
- Dissertations Abstracts International. 87-06B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520260202105708
■006m o d
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■020 ▼a9798270223151
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■035 ▼a(MiAaPQ)OhioLINK:osu1724022928335753
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616
■1001 ▼aStubbs, Toneisha Decarla.
■24510▼aLocalization of G Protein Coupled Receptors to Primary Cilia and Its Impact on Neuronal Function
■260 ▼a[Sl]▼bThe Ohio State University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a156 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-06, Section: B.
■500 ▼aAdvisor: Mykytyn, Kirk.
■5021 ▼aThesis (Ph.D.)--The Ohio State University, 2024.
■520 ▼aThe primary cilium, a microtubule-based organelle extending from the cell body, has emerged as a pivotal player in cellular homeostasis and disease pathology. Dysfunction in proteins associated with ciliary function leads to ciliopathies, a group of disorders affecting multiple organ systems, including the central nervous system (CNS). Despite the well-established roles of primary cilia in sensory functions, their significance in neuronal processes remains incompletely understood. This dissertation investigates the localization and function of G protein-coupled receptors (GPCRs) within primary cilia, particularly focusing on the dopamine receptor 1 (D1) and its implications for neuronal signaling and behavior.Chapter 2 introduces a novel constitutive Bardet-Biedl Syndrome (BBS) mouse model, to explore the impact of BBSome dysfunction on GPCR ciliary localization. Our findings reveal disrupted localization of select GPCRs in response to BBSome loss, emphasizing the crucial role of BBS proteins in establishing ciliary GPCR pathways.Chapter 3 examines the consequences of disrupting D1 ciliary localization in D1- expressing neurons. Employing loss of Bbs1 or cilia, we observe obesity associated with reduced locomotor activity, indicating diminished D1 signaling in the CNS and underscoring the importance of neuronal cilia in GPCR signaling regulation.Chapter 4 presents transcriptomic data of the D1Bbs1+/- and D1Cilia+/- mouse lines, revealing that the loss of Bbs1 or the loss of cilia on D1-expression neurons leads to changes in gene expression. We validate a novel transgenic mouse model to resolve the D1 protein association network. In this D1-APEX2 mouse model, the localization, activation, and signaling of D1-APEX2 is equivalent to wildtype D1. Proximity labeling of Bbs4+/+ and Bbs4-/- striatal lysates reveals that the loss of Bbs4 impacts D1 protein associations.Chapter 5 presents proteomics data using proximity labeling in a D1-APEX2 mouse model to examine the D1 protein association network. Through proximity labeling, we identify known interactors of the D1 receptors and proteins involved in canonical and noncanonical signaling pathways, suggesting the existence of a signaling hub for D1.Overall, this work advances our understanding of cilia biology and GPCR signaling, shedding light on the role of primary cilia in neuronal function and its implications for disease pathology.
■590 ▼aSchool code: 0168.
■650 4▼aNeurosciences
■650 4▼aCellular biology
■650 4▼aPathology
■650 4▼aMolecular biology
■653 ▼aDopamine
■653 ▼aG protein-coupled receptors
■653 ▼aPrimary cilia
■653 ▼aBardet-Biedl Syndrome
■653 ▼aDisease pathology
■690 ▼a0317
■690 ▼a0379
■690 ▼a0307
■690 ▼a0571
■71020▼aThe Ohio State University▼bNeuroscience Graduate Studies Program.
■7730 ▼tDissertations Abstracts International▼g87-06B.
■790 ▼a0168
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17361112▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
