DCHS1, Lix1L, and the Septin Cytoskeleton: Molecular and Developmental Etiology of Mitral Valve Prolapse
Year: 2022
Type: article
Abstract: 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.
DOI: 10.3390/jcdd9020062
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,885
Awards: Cilia and Valvular Heart Disease, Molecular and cellular causes of mitral valve prolapse, G167217301, G350062807, Turning mechanisms of heart development into remedial therapies for heart valvuloseptal defects, G4915442529, G5103928679, Genetic and Molecular Determinants of Bicuspid and Calcific Aortic Valve Disease, G547628071, G5743453972, Bioengineering Center of Regeneration and Formation of Tissues (SC BioCRAFT), Primary Cilia and Mitral Valve Prolapse, Training To Improve Cardiovascular Therapies, EXTRAMURAL RESEARCH FACILITIES CONSTRUCTION, G6569058183, G6781035106, Targeting Mek/Erk Signaling in the Treatment of Mitral Valve Prolapse, Cardiac Tauopathy: a developmental cilia defect?, Dzip1 and Mitral Valve Prolapse, G8302684942, G9000001279, G9000018733, G9000033182, G9000114222, G9000185643, G9000210174, G9000328393
OpenAlex ID: W4213254244