时间标签：数据日期 2026-11-05 · 生成时间 2026-11-05 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/11/02 – 2026/11/06 ｜ 情报发生日期 2026-11-05
研究问题
However, the precise structural transitions of the ADGRV1 GAIN domain following autoproteolysis, the regulatory factors controlling Stachel accessibility, and whether activation requires complete NTF-CTF separation remain unclear.；However, whether these interactions directly induce NTF-CTF dissociation and activate ADGRV1 remains to be experimentally determined.Force-mediated activation via NTF-CTF dissociationIn most aGPCRs, GPS autoproteolysis produces a metastable, noncovalent NTF-CTF complex, which can be dissociated by mechanical forces or ECM interaction, thereby exposing the Stachel motif in some well-characterizied cases [64, 66].；For ECM-associated aGPCRs, ligand binding may provide the initial extracellular attachment, whereas mechanical tension determines whether sufficient conformational energy is transmitted to the receptor to induce activation [66, 67].
方法
By synthesizing current findings, we seek to establish a theoretical framework that advances biomedical research and opens new avenues for clinical applications and therapeutic development.Structural features of ADGRV1 ADGRV1 has been studied extensively since its initial cloning from human brain cDNA in the late 1990s [22, 23].；Importantly, numerous disease-associated variants of ADGRV1 have been identified, particularly in patients with USH, neurological disorder diseases and other sensory disorders, highlighting the functional significance of its structural organization and facilitating the interpretation of pathogenic mutations [28, 31].；However, GPS-mediated cleavage requires the intact structural context of the GAIN domain, as the isolated GPS sequence alone is not sufficient to undergo efficient autoproteolysis [44].
核心结论
Although the direct experimental evidence of ADGRV1 is currently limited, its predicted PBM suggests that similar PDZ-dependent regulatory mechanisms may appliable.In summary, ADGRV1 is a multifunctional receptor with structure and its modular architecture, Calx-β motifs for calcium treatment, LamG/PTX and EPTP/EAR domains for adhesion and mechanosensing, GAIN/GPS module and Stachel motif for proteolytic regulation, 7TM core for canonical GPCR signaling, and PBM for PDZ-mediated trafficking, which all underpin a broad repertoire of physiological functions (Fig. 1).；In this context, the fundamental difference in signaling potential between membrane-bound isoforms (a and b) and soluble isoform (c) suggests a possible mechanism by which alternative splicing can diversify the function of ADGRV1 in the cellular environments.In summary, alternative splicing is a major source of structural heterogeneity of ADGRV1, primarily affecting the composition of its extensive ECD, and in some cases, eliminating transmembrane and cytoplasmic regions.；Although only a subset of splice isoforms has been structurally characterized, available genetic and cellular evidence indicates that isoform-specific domain architecture constrains signaling capacity and cellular context.
局限
However, GPS-mediated cleavage requires the intact structural context of the GAIN domain, as the isolated GPS sequence alone is not sufficient to undergo efficient autoproteolysis [44].；However, the precise structural transitions of the ADGRV1 GAIN domain following autoproteolysis, the regulatory factors controlling Stachel accessibility, and whether activation requires complete NTF-CTF separation remain unclear.；Thus, elucidation of these regulatory mechanisms represents an important direction for future studies.
对本项目的价值
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全文来源
PubMed PMC JATS（正文 54,383 字符，题名指纹 0.91，已过 PubMed PMCID 官方关联 + 题名指纹 + 正文长度归属校验）
原文题录
- 中文题名：ADGRV1 的结构特征与疾病相关功能：信号机制洞见
- 英文标题：Structural features and disease-associated functions of ADGRV1: insights from signaling mechanisms.
- 期刊与标识：Cell communication and signaling : CCS · PMID 42972392 · DOI 10.1186/s12964-026-03149-8 · PMC PMC13729602