Septins are a conserved family of GTP-binding proteins that self-assemble into defined hetero-oligomeric complexes that are able to polymerize to form filaments and other supramolecular arrangements. Septin structures associate with biological membranes by interacting with specific lipids, and are involved in cellular compartmentalization and a variety of membrane remodeling events. Septins are essential in cell division, where they play a number of functional roles, as well as in cellular differentiation Furthermore, septins have been associated with a variety of cancers on the basis of alterations of their expression in solid tumors or translocations in leukemias. Also, expression changes in septins have been implicated in neuropathological conditions, such as Alzheimer's and Parkinson's disease, as well as retinopathies, and mutations in SEPT9 are the cause of hereditary neuralgic amyotrophy (HNA). Yet, little is known about the molecular mechanisms that govern septin organization and function. Further functional characterization of septins is clearly crucial to our understanding of their possible diagnostic, prognostic, and therapeutic applications. For example, what is the nature of the interactions among different septin forms that give rise to polymers with different functional properties? What is the interplay between septin assembly and their interaction with membrane phosphoinositides? What is the organization of septin structures in situ? How do the post- translational modifications that septins undergo influence their properties? How do septins interact with and affect other cellular regulators and cytoskeletal elements? We will address these questions using budding yeast as a model system. Understanding how septin assembly is regulated in this model eukaryotic organism may offer new insights about how aberrant septin structures contribute to malignancy and disease.
Septins are conserved eukaryotic proteins that self-associate, polymerize into filaments, interact with membranes, and are required for membrane remodeling events, from cell division to differentiation. Pronounced up-regulation of certain splice variants f the septin SEPT9 is a hallmark of breast and ovarian cancers and other tumor types. Expression changes in septins have also been associated with neuropathological conditions. Understanding how septin assembly is regulated in our model system will offer new insights about how aberrant septin structures contribute to disease.
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