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.
Highlights
Discovered in 1971, septins are highly conserved GTP-binding and self-assembling filamentous proteins [1,2]
In the 40 years of research following Hartwell’s discovery, septins were identified in many eukaryotic organisms, and we understand the evolution of septin genes and their encoded proteins
As a result of their diverse interactions with actin, microtubules, integrins and other cytoskeleton-binding proteins, septins are considered the fourth component of the cytoskeleton
Summary
Discovered in 1971, septins are highly conserved GTP-binding and self-assembling filamentous proteins [1,2]. Through cell division screens using the budding yeast Saccharomyces cerevisiae, Hartwell was the first to identify septins as essential genes for cytokinesis and cell polarity [2,3]. In the 40 years since, septins have been identified in many other organisms, including Drosophila, mice and humans, and have been implicated in a plethora of developmental and disease processes. Emerging as important regulators of the cytoskeleton, pathways that rely on septins present exciting avenues across various fields. In this review, we have summarized the knowledge of septin biology far and provided perspectives on their involvement in various developmental and acquired cardiac diseases
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