Tugging at the Heart Strings: The Septin Cytoskeleton in Heart Development and Disease

Abstract

Septin genes were originally identified in budding yeast in 1971. Since their original discovery, at least 13 mammalian genes have now been found, which give rise to a vast array of alternatively spliced proteins that display unique spatial-temporal function across organs systems. Septin’s are now recognized as the 4th major component of the cytoskeleton. Their role in regulating ciliogenesis, actin and microtubule organization and their involvement in mechanotransduction clearly solidify their place as both a responder and driver of cellular activity. Although work on septin’s has escalated over the past decades, knowledge of septin function in the heart remains rudimentary. Whereas many cardiovascular diseases have been associated with genetic loci that include septin genes, new and additional concerted efforts will likely uncover previously unrecognized mechanisms by which the septin class of proteins contribute to clinical cardiac phenotypes. In this review, we place known function of septin proteins in the context of heart development and disease and provide perspectives on how increased knowledge of these proteins can mechanistically inform cardiac pathologies.

DCHS1, Lix1L, and the Septin Cytoskeleton: Molecular and Developmental Etiology of Mitral Valve Prolapse

“…Septins have been identified in various cellular processes including polarity, mechanotransduction, ciliogenesis and axon growth, among others [23]. As a result, septins have been identified in various diseases, but remain vastly understudied in the context of cardiac development and disease [24]. Figure S3 illustrates the RNA expression of septins 2, 5, 6, 7, 8, 9 and 11 supporting their presence during heart development.…”

Advances in 3D bioprinting technology for cardiac tissue engineering and regeneration

“…Moreover, the use of additional current to stimulate the printed structure could be measured in response to changes in the calcium flow, providing good support for the discovery of new specific calmodulin genes related to heart regeneration [ 86 ]. Seemingly, in addition to being used as a patch or graft, the dynamic monitoring of 3D-CTE-OCR can potentially act in a subsidiary role in the in vitro study of regulatory molecular mechanisms towards cardiac development and disease [ 156 , 157 ].…”

Primary Cilia and Their Role in Acquired Heart Disease

“…Mutations in these proteins have been associated with a variety of ciliopathies [17]. Numerous other membrane-bound proteins located along the cilia have been associated with ciliopathies as well, including polycystins, known for causing autosomal dominant polycystic kidney disease, and septins, which have been linked with a variety of cancers and neurodegenerative conditions [20][21][22][23][24][25].…”