Conquering the complex world of human septins: implications for health and disease

• Published in: Clinical genetics Vol. 77; no. 6; pp. 511 - 524
• Main Authors: Peterson, EA, Petty, EM
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2010; Wiley-Blackwell
• Subjects: Alzheimer Disease - metabolism; Amino Acid Sequence; Biological and medical sciences; cancer; cell division; Cellular biology; Disease; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genetics; Genetics of eukaryotes. Biological and molecular evolution; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; GTPases; human septins; Humans; Medical genetics; Medical research; Medical sciences; Molecular and cellular biology; Molecular Sequence Data; Mutation; Neoplasms - metabolism; Nervous System Diseases - metabolism; neurological disorders; Phylogeny; Proteins; SEPT9; Septin; World; Human; Nervous system diseases; Disease; Enzyme; Triphosphoric monoester hydrolases; Health; GTPases; Cell division; dGTPase; Esterases; Malignant tumor; Complexes; SEPT9; human septins; neurological disorders; Hydrolases; Genetics; Neurological disorder; Cancer
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2010.01392.x

Peterson EA and Petty EM. Conquering the complex world of human septins: implications for health and disease. Septins are highly conserved filamentous proteins first characterized in budding yeast and subsequently identified in must eukaryotes. Septins can bind and hydrolyze GTP, which is intrinsically related to their formation of septin hexamers and functional protein interactions. The human septin family is composed of 14 loci, SEPT1‐SEPT14, which encode dozens of different septin proteins. Their central GTPase and polybasic domain regions are highly conserved but they diverge in their N‐terminus and/or C‐terminus. The mechanism by which the different isoforms are generated is not yet well understood, but one can hypothesize that the use of different promoters and/or alternative splicing could give rise to these variants. Septins perform diverse cellular functions according to tissue expression and their interacting partners. Functions identified to date include cell division, chromosome segregation, protein scaffolding, cellular polarity, motility, membrane dynamics, vesicle trafficking, exocytosis, apoptosis, and DNA damage response. Their expression is tightly regulated to maintain proper filament assembly and normal cellular functions. Alterations of these proteins, by mutation or expression changes, have been associated with a variety of cancers and neurological diseases. The association of septins with cancer results from alterations of expression in solid tumors or translocations in leukemias [mixed lineage leukemia (MLL)]. Expression changes in septins have also been associated with neurological conditions such as Alzheimer's and Parkinson's disease, as well as retinopathies, hepatitis C, spermatogenesis and Listeria infection. Pathogenic mutations of SEPT9 were identified in the autosomal dominant neurological disorder hereditary neuralgic amyotrophy (HNA). Human septin research over the past decade has established their importance in cell biology and human disease. Further functional characterization of septins is crucial to our understanding of their possible diagnostic, prognostic, and therapeutic applications.