Control of cortical rigidity by the cytoskeleton: Emerging roles for septins

Abstract

The cortex is the outermost region of the cell, comprising all of the elements from the plasma membrane to the cortical actin cytoskeleton that cooperate to maintain the cell's shape and topology. In eukaryotes without cell walls, this cortex governs the contact between their plasma membranes and the environment and thereby influences cell shape, motility, and signaling. It is therefore of considerable interest to understand how cells control their cortices, both globally and with respect to small subdomains. Here we review the current understanding of this control, including the regulation of cell shape by balances of outward hydrostatic pressure and cortical tension. The actomyosin cytoskeleton is the canonical regulator of cortical rigidity and indeed many would consider the cortex to comprise the actin cortex nearly exclusively. However, this actomyosin array is intimately linked to the membrane, for example via ERM and PIP2 proteins. Additionally, the lipid membrane likely undergoes rigidification by other players, such as Bin-Amphiphysin-Rvs proteins. Recent data also indicates that the septin cytoskeleton may play a formidable and more direct role in stabilization of membranes, particularly in contexts where cells receive limited external stabilization from their environments. Here, we review how septins may play this role, drawing on their physical form, their ability to directly bind and modify membranes and actomyosin, and their interactions with vesicular machinery. Deficiencies and alterations in the nature of the septin cytoskeleton may thus be relevant in multiple disease settings. V C 2010 WileyLiss, Inc.Key Words: septin, cortical tension, cell motility, actin IntroductionT he rigidity of the cortex is a fundamental property of all cells, and in metazoans, where the nature of each contact between a cell and its neighbor or substrate is critical to complex biology, cortical rigidity plays particularly interesting and important roles. Specialized cellular function is supported by the regulation of interactions between cortical elements, which ensures mechanical stability and flexibility of the cortex. For instance, stable contacts between cells, such as tight junctions, can be encouraged by long-lived, highly rigid cortical structures [Van Itallie et al., 2009]. Alternatively, locally rigid regions can be dynamically coordinated to promote motility. At the simplest level, a critical difference between stable and motile cells is the rapidity with which their membranes are able to locally contort and promote access between receptors and ligands. This deformability may be grossly referred to as ''cortical rigidity''-the importance of which also extends to include the regulation of cell shape, cytokinesis, development, and the response to a changing external environment. Although cortical rigidity and the cortex is often used to invoke features of the actin cytoskeleton, this review aims not to restrict only to that framework but to consider the cortex as a sum of actin as well as other participants. A...

The Septin AspB in Aspergillus nidulans Forms Bars and Filaments and Plays Roles in Growth Emergence and Conidiation

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Recruitment of septin cytoskeletal proteins by Botulinum toxin A protease determines its remarkable stability

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“…By also interacting with actins and tubulins, septins serve as linkers between the plasma membrane and the intracellular cytoskeleton (Gilden and Krummel, 2010). In addition, by binding to other proteins, they act as diffusion barriers important for defining specific membrane compartments and for localizing interacting proteins at specific intracellular sites (Gilden and Krummel, 2010;Hall and Russell, 2012;Mostowy and Cossart, 2012;Nakahira et al, 2010;Saarikangas and Barral, 2011;Spiliotis et al, 2008). Septins are known to form membrane-associated hetero-oligomeric structures, such as rings and filaments (Gilden and Krummel, 2010;Hall and Russell, 2012;Kinoshita, 2003;Mostowy and Cossart, 2012).…”