DCHS1, Lix1L, and the Septin Cytoskeleton: Molecular and Developmental Etiology of Mitral Valve Prolapse.
DCHS1, Lix1L, and the Septin Cytoskeleton: Molecular and Developmental Etiology of Mitral Valve Prolapse.
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DOI：
10.3390/jcdd9020062
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发表时间：
2022-02-17
影响因子：
2.4
通讯作者：
Norris RA
中科院分区：
文献类型：
--
作者：
Moore KS;Moore R;Fulmer DB;Guo L;Gensemer C;Stairley R;Glover J;Beck TC;Morningstar JE;Biggs R;Muhkerjee R;Awgulewitsch A;Norris RA
二尖瓣脱垂（MVP）是一种常见的心脏瓣膜疾病，经常发展为严重的继发性并发症，需要手术治疗。在成人环境中，MVP表现为细胞外基质紊乱和生物力学不正常的组织。然而，MVP最近被证明具有发育基础，因为在胚胎发育过程中已经确定了多个致病基因表达。早在出生时就在具有人类MVP突变的小鼠模型中观察到疾病表型。这项研究的重点是DCHS1的发育功能，DCHS1是第一个在多个非综合征性MVP家庭中被证明是病因的基因之一。通过使用各种生化技术以及小鼠和细胞培养模型，我们通过与细胞质蛋白Lix1-Like （LIX1L）的相互作用，证明了基于dchs1的细胞粘附与septin-actin细胞骨架之间的独特联系。DCHS1-LIX1L-SEPT9轴与丝状肌动蛋白相互作用并促进丝状肌动蛋白组织，从而指导细胞- ecm排列和瓣膜组织形状。
Mitral valve prolapse (MVP) is a common cardiac valve disease that often progresses to serious secondary complications requiring surgery. MVP manifests as extracellular matrix disorganization and biomechanically incompetent tissues in the adult setting. However, MVP has recently been shown to have a developmental basis, as multiple causal genes expressed during embryonic development have been identified. Disease phenotypes have been observed in mouse models with human MVP mutations as early as birth. This study focuses on the developmental function of DCHS1, one of the first genes to be shown as causal in multiple families with non-syndromic MVP. By using various biochemical techniques as well as mouse and cell culture models, we demonstrate a unique link between DCHS1-based cell adhesions and the septin-actin cytoskeleton through interactions with cytoplasmic protein Lix1-Like (LIX1L). This DCHS1-LIX1L-SEPT9 axis interacts with and promotes filamentous actin organization to direct cell-ECM alignment and valve tissue shape.
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影响因子：
2.9
作者：
de Vlaming, Annemarieke;Sauls, Kimberly;Hajdu, Zoltan;Visconti, Richard P.;Mehesz, Agnes Nagy;Levine, Robert A.;Slaugenhaupt, Susan A.;Hagege, Albert;Chester, Adrian H.;Markwald, Roger R.;Norris, Russell A.
通讯作者：
Norris, Russell A.
影响因子：
64.8
作者：
Durst R;Sauls K;Peal DS;deVlaming A;Toomer K;Leyne M;Salani M;Talkowski ME;Brand H;Perrocheau M;Simpson C;Jett C;Stone MR;Charles F;Chiang C;Lynch SN;Bouatia-Naji N;Delling FN;Freed LA;Tribouilloy C;Le Tourneau T;LeMarec H;Fernandez-Friera L;Solis J;Trujillano D;Ossowski S;Estivill X;Dina C;Bruneval P;Chester A;Schott JJ;Irvine KD;Mao Y;Wessels A;Motiwala T;Puceat M;Tsukasaki Y;Menick DR;Kasiganesan H;Nie X;Broome AM;Williams K;Johnson A;Markwald RR;Jeunemaitre X;Hagege A;Levine RA;Milan DJ;Norris RA;Slaugenhaupt SA
通讯作者：
Slaugenhaupt SA
DOI：
10.1016/j.bbrc.2016.04.036
发表时间：
2016-05-13
影响因子：
3.1
作者：
Dau, Cecile;Fliegauf, Manfred;Braun, Gerald S.
通讯作者：
Braun, Gerald S.
影响因子：
5.2
作者：
Cellini, Elena;Vetro, Annalisa;Guerrini, Renzo
通讯作者：
Guerrini, Renzo
影响因子：
4.6
作者：
Gammie, James S.;Chikwe, Joanna;Quinn, Rachael W.
通讯作者：
Quinn, Rachael W.