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The state of the septin cytoskeleton from assembly to function Benjamin L. Woods1 and Amy S. Gladfelter1,2 Abstract
Septins are conserved guanine nucleotide-binding proteins that polymerize into filaments at the cell cortex or in association with other cytoskeletal proteins, such as actin or microtubules. As integral players in many morphogenic and signaling events, septins form scaffolds important for the recruitment of the cytokinetic machinery, organization of the plasma membrane, and orientation of cell polarity. Mutations in septins or their misregulation are associated with numerous diseases. Despite growing appreciation for the importance of septins in different aspects of cell biology and disease, septins remain relatively poorly understood compared with other cytoskeletal proteins. Here in this review, we highlight some of the recent developments of the last two years in the field of septin cell biology. Addresses 1 Biology Department, University of North Carolina, Chapel Hill, NC, 27599, USA 2 Marine Biological Laboratory, Woods Hole, MA, 02543, USA Corresponding author: Gladfelter, Amy S ([email protected])
Current Opinion in Cell Biology 2021, 68:105–112 This review comes from a themed issue on Cell Architecture Edited by Pekka Lappalainen and Pierre Coulombe For a complete overview see the Issue and the Editorial
https://doi.org/10.1016/j.ceb.2020.10.007 0955-0674/© 2020 Published by Elsevier Ltd.
Keyword Amphipathic helix (AH) domain.
Introduction Septins are found in many eukaryotes including fungi and metazoans but missing in land plants. The basic unit of septins are nonpolar, hetero-oligomers 17e32 nm long (depending on the species, see Figure 1), which polymerize into larger filaments by annealing end-toend at the plasma membrane [1e3]. Filaments can be organized into a variety of distinct, higher-order assemblies such as bundles, lattices, rings, and bars each of which have different functions in different cellular contexts [4,5]. Higher-order septin assemblies act as scaffolds for microtubules and F-actin, regulate cell www.sciencedirect.com
morphogenesis, recognize micron-scaled membrane curvature, and organize the plasma membrane [6]. Septins have been implicated in a range of cellular processes including cell division, cell migration, ciliogenesis, and neuronal branching [7e11]. Given their varied cellular functions, a growing body of literature implicates septins in various diseases including cancer [12e14]. Septins are finding new prominence and importance in diverse cell functions including neuronal signaling, fertility, and immunity. Several new studies have expanded the role of septins in neuronal signal transduction. Calcium signaling and homeostasis are dependent on septin regulation of calcium-entry channels at the plasma membrane in neurons [15,16]. Moreover, disruption of septins in neurons delays neurotransmitter release in mice through a separate, calcium signalinge independent mechanism [17]. Another recent study in mice demonstrated that septins are important
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