Gonadotropin Receptor Dimerization/Oligomerization

促性腺激素受体二聚化/寡聚化

• 批准号: 7476324
• 负责人: DEBORAH SEGALOFF
• 金额: $ 23.99万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7476324
• 关键词: Address; Applications Grants; Arrestin; Arrestins; Binding; Biological Process; Bioluminescence; Cell surface; Cells; Complex; Consensus; Cytoplasmic Tail; Data; Dimerization; Extracellular Domain; Family; Follicle Stimulating Hormone Receptor; G-Protein-Coupled Receptors; Glycoproteins; Gonadotropin Receptors; Grant; Helix (Snails); Heterodimerization; Homo; Homodimerization; Hormone Receptor; LH Receptors; Laboratories; Leucine-Rich Repeat; Maps; Mediating; Methods; Molecular Weight; Numbers; Phosphorylation; Physiological; Play; Publishing; Reporting; Reproductive Endocrinology; Reproductive Physiology; Role; Techniques; Testing; Thyrotropin Receptor; Transmembrane Domain; dimer; ear helix; granulosa cell; insight; member; novel; novel strategies; protein protein interaction; receptor; receptor internalization

DESCRIPTION (provided by applicant): The LH receptor (LHR) and FSH receptor (FSHR), collectively termed the gonadotropin receptors, are GPCRs that play a pivotal role in reproductive physiology. Recent studies from our laboratory and others suggest that the LHR self-associates into high molecular weight complexes consistent with dimers and oligomers of the receptor. The focus of this grant is to mechanistically and functionally examine the dimerization/oligomerization of the hLHR as well as the closely related hFSHR. In spite of the growing body of evidence that GPCRs exist as dimers/oligomers, the region(s) of a given GPCR mediating dimerization appear varied and the functional role(s) of the dimers/oligomers remains enigmatic. We propose to utilize novel and complementary approaches to address these questions as they relate to gonadotropin receptor dimerization/oligomerization. In addition, given the precedence for hetero-dimerization/oligomerization between different GPCRs, the high degree of homology between the hLHR and hFSHR, and the expression of both the hLHR and hFSHR in differentiated granulosa cells, a particularly relevant question we will also address is whether the hLHR and hFSHR form hetero-dimers/oligomers and what the functional ramifications of this are. The specific aims of the grant, therefore, are to: (1) determine the functional role(s) of cell surface gonadotropin receptor dimerization; (2) determine if the hLHR and hFSHR hetero-dimerize and, if so, examine the functional consequences of this phenomenon; and (3) determine the structural region(s) mediating homo- and hetero-dimerization of the gonadotropin receptors. Overall, the proposed studies in the grant will contribute novel and significant insights into homo- and heterodimerization/oligomerization of the gonadotropin receptors, providing new paradigms for the roles of these receptors in reproductive endocrinology.

描述（由申请方提供）：LH受体（LHR）和FSH受体（FSHR）统称为促性腺激素受体，是在生殖生理学中发挥关键作用的GPCR。我们实验室和其他实验室最近的研究表明，LHR自缔合成与受体的二聚体和寡聚体一致的高分子量复合物。这项研究的重点是从机制和功能上研究hLHR以及密切相关的hFSHR的二聚化/寡聚化。尽管越来越多的证据表明GPCR作为二聚体/寡聚体存在，但给定GPCR的介导二聚化的区域似乎是变化的，并且二聚体/寡聚体的功能作用仍然是谜。我们建议利用新的和互补的方法来解决这些问题，因为它们涉及促性腺激素受体二聚化/寡聚化。此外，考虑到不同GPCR之间异源二聚化/寡聚化的优先性，hLHR和hFSHR之间的高度同源性，以及hLHR和hFSHR在分化的颗粒细胞中的表达，我们还将解决的一个特别相关的问题是hLHR和hFSHR是否形成异源二聚体/寡聚体，以及其功能分支是什么。因此，该基金的具体目的是：（1）确定细胞表面促性腺激素受体二聚化的功能作用;（2）确定hLHR和hFSHR是否异源二聚化，如果是，检查这种现象的功能后果;（3）确定介导促性腺激素受体同源和异源二聚化的结构区域。总的来说，在补助金中提出的研究将有助于新的和重要的见解，同源和异源二聚化/寡聚化的促性腺激素受体，提供新的范例，这些受体在生殖内分泌学的作用。