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Investigating Regulators of Ciliary Composition and Feeding Behavior in the Paraventricular Nucleus
Investigating Regulators of Ciliary Composition and Feeding Behavior in the Paraventricular Nucleus
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202103210
- ISBN
- 9798280729834
- DDC
- 574
- 서명/저자
- Investigating Regulators of Ciliary Composition and Feeding Behavior in the Paraventricular Nucleus
- 발행사항
- [Sl] : University of California, San Francisco, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 103 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- 주기사항
- Advisor: Reiter, Jeremy;Ashrafi, Kaveh.
- 학위논문주기
- Thesis (Ph.D.)--University of California, San Francisco, 2025.
- 초록/해제
- 요약Bardet-Biedl syndrome (BBS) is a ciliopathy, one of the hallmarks of which is obesity. We investigated the origins of obesity in BBS using mice with disruptions in Bbs1 or Bbs4, two BBS-associated genes. Within the paraventricular nucleus (PVN) of the hypothalamus, disruption of either gene increased the ciliary localization of the Melanocortin 4 Receptor (MC4R), a GPCR that acts at neuronal cilia to regulate long-term energy homeostasis. MC4R is proposed to signal through adenylyl cyclase 3 (AC3) and activation of PKA. We found that disruption of Bbs1 or Bbs4 decreased ciliary levels of AC3. Inhibiting PKA in a cell model increased AC3 cilia localization, suggesting that PKA negatively regulates the ciliary localization of its upstream activator AC3. Indeed, reducing PKA activity by expressing a constitutively ciliary form of Smoothened in the hypothalamus increased ciliary AC3 and caused obesity. Therefore, PKA restrains ciliary AC3 levels and ciliary PKA activity in hypothalamic neurons is anorexigenic. Our data further suggests that, in BBS, reduced levels of AC3 in PVN neuronal cilia causes obesity.
- 일반주제명
- Cellular biology
- 일반주제명
- Physiology
- 일반주제명
- Neurosciences
- 일반주제명
- Molecular biology
- 일반주제명
- Genetics
- 키워드
- Brain
- 키워드
- Cilia
- 키워드
- Feeding behavior
- 키워드
- GPCR
- 키워드
- Neuron
- 키워드
- Obesity
- 기타저자
- University of California, San Francisco Biochemistry and Molecular Biology
- 기본자료저록
- Dissertations Abstracts International. 86-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798280729834
■035 ▼a(MiAaPQ)AAI32001084
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aCanales, Gabriela Isla-Inez.▼0(orcid)0000-0002-4219-4195
■24510▼aInvestigating Regulators of Ciliary Composition and Feeding Behavior in the Paraventricular Nucleus
■260 ▼a[Sl]▼bUniversity of California, San Francisco▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a103 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: B.
■500 ▼aAdvisor: Reiter, Jeremy;Ashrafi, Kaveh.
■5021 ▼aThesis (Ph.D.)--University of California, San Francisco, 2025.
■520 ▼aBardet-Biedl syndrome (BBS) is a ciliopathy, one of the hallmarks of which is obesity. We investigated the origins of obesity in BBS using mice with disruptions in Bbs1 or Bbs4, two BBS-associated genes. Within the paraventricular nucleus (PVN) of the hypothalamus, disruption of either gene increased the ciliary localization of the Melanocortin 4 Receptor (MC4R), a GPCR that acts at neuronal cilia to regulate long-term energy homeostasis. MC4R is proposed to signal through adenylyl cyclase 3 (AC3) and activation of PKA. We found that disruption of Bbs1 or Bbs4 decreased ciliary levels of AC3. Inhibiting PKA in a cell model increased AC3 cilia localization, suggesting that PKA negatively regulates the ciliary localization of its upstream activator AC3. Indeed, reducing PKA activity by expressing a constitutively ciliary form of Smoothened in the hypothalamus increased ciliary AC3 and caused obesity. Therefore, PKA restrains ciliary AC3 levels and ciliary PKA activity in hypothalamic neurons is anorexigenic. Our data further suggests that, in BBS, reduced levels of AC3 in PVN neuronal cilia causes obesity.
■590 ▼aSchool code: 0034.
■650 4▼aCellular biology
■650 4▼aPhysiology
■650 4▼aNeurosciences
■650 4▼aMolecular biology
■650 4▼aGenetics
■653 ▼aBrain
■653 ▼aCilia
■653 ▼aFeeding behavior
■653 ▼aGPCR
■653 ▼aNeuron
■653 ▼aObesity
■690 ▼a0379
■690 ▼a0317
■690 ▼a0369
■690 ▼a0307
■690 ▼a0719
■71020▼aUniversity of California, San Francisco▼bBiochemistry and Molecular Biology.
■7730 ▼tDissertations Abstracts International▼g86-12B.
■790 ▼a0034
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357343▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
