The Caenorhabditis elegans septin complex is nonpolar

John, Corinne; Hite, Richard K; Weirich, Christine S.; Fitzgerald, Daniel J.; Jawhari, Hatim; Faty, Mahamadou; Schläpfer, Dominik; Kroschewski, Ruth; Winkler, Fritz K.; Walz, Thomas; Barral, Yves; Steinmetz, Michel O.

doi:10.1038/sj.emboj.7601775

Cited by 140 publications

(155 citation statements)

References 53 publications

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“…It has been demonstrated that most septins present a C-terminal domain predicted to form a dimeric coiled coil whose function remains elusive (11)(12)(13)(14). The hallmark of a coiled coil is a repeating amino acid heptad pattern (a, b, c, d, e, f, and g) in which residues in positions a and d tend to be hydrophobic while those in positions e and g tend to be polar or charged.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies reported the importance of C-terminal interactions between septins of the SEPT6 and SEPT7 groups in diverse organisms (11,13,18), suggesting that they might form a coiled coil that would lend stability and/or play a role in determining preferential interaction between different septins in physiologically relevant filaments.…”

Section: Introductionmentioning

confidence: 99%

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Heterotypic Coiled-Coil Formation is Essential for the Correct Assembly of the Septin Heterofilament

Sala

Valadares

Macêdo

et al. 2016

Biophysical Journal

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Protein-protein interactions play a critical role in promoting the stability of protein quaternary structure and in the assembly of large macromolecular complexes. What drives the stabilization of such assemblies is a central question in biology. A limiting factor in fully understanding such systems is the transient nature of many complexes, making structural studies difficult. Septins comprise a conserved family of guanine nucleotide binding proteins that polymerize in the form of heterofilaments. In structural terms, they have a common organization: a central GTPase domain, an N-terminal domain, and a C-terminal domain; the latter is predicted to form a coiled coil. Currently, even for the best characterized human septin heterocomplex (SEPT2/SEPT6/SEPT7), the role of C-terminal domain is not fully established, and this is partly due to the absence of electron density for the C-terminal domains in the x-ray structure. Here we present results on the homo/heterotypical affinity for the C-terminal domains of human septins belonging to the SEPT6 and SEPT7 groups (SEPT6C/8C/10C/11C and SEPT7C, respectively) and provide clear evidence that this domain determines the preference for heterotypic interactions at one specific interface during the assembly of the heterofilament. This observation has wider implications where macromolecular assemblies are defined by coiled-coil protein interactions.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Heterotypic Coiled-Coil Formation is Essential for the Correct Assembly of the Septin Heterofilament

Sala

Valadares

Macêdo

et al. 2016

Biophysical Journal

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“…Proteins of this family are ubiquitous in fungal and animal cells and typically localize to the cell cortex, where they appear to serve as scaffolds and diffusion barriers for other proteins that participate in a wide variety of cellular processes (Longtine et al 1996;Gladfelter et al 2001;Hall et al 2008;Caudron and Barral 2009). Despite the recent progress in elucidating the mechanisms of septin assembly ( John et al 2007;Sirajuddin et al 2007;Bertin et al 2008;McMurray and Thorner 2008), the details of septin function remain obscure. However, one prominent role of the septins and associated proteins is in cytokinesis.…”

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confidence: 99%

Cooperation Between the Septins and the Actomyosin Ring and Role of a Cell-Integrity Pathway During Cell Division in Fission Yeast

Wang

et al. 2010

Genetics

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A major question about cytokinesis concerns the role of the septin proteins, which localize to the division site in all animal and fungal cells but are essential for cytokinesis only in some cell types. For example, in Schizosaccharomyces pombe, four septins localize to the division site, but deletion of the four genes produces only a modest delay in cell separation. To ask if the S. pombe septins function redundantly in cytokinesis, we conducted a synthetic-lethal screen in a septin-deficient strain and identified seven mutations. One mutation affects Cdc4, a myosin light chain that is an essential component of the cytokinetic actomyosin ring. Five others cause frequent cell lysis during cell separation and map to two loci. These mutations and their dosage suppressors define a signaling pathway (including Rho1 and a novel arrestin) for repairing cell-wall damage. The seventh mutation affects the poorly understood RNAbinding protein Scw1 and severely delays cell separation when combined either with a septin mutation or with a mutation affecting the septin-interacting, anillin-like protein Mid2, suggesting that Scw1 functions in a pathway parallel to that of the septins. Taken together, our results suggest that the S. pombe septins participate redundantly in one or more pathways that cooperate with the actomyosin ring during cytokinesis and that a septin defect causes septum defects that can be repaired effectively only when the cellintegrity pathway is intact.

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“…Structural analyses of worm and mammalian septins have revealed that the heteromeric, rod-shaped complex is conserved (19)(20)(21). Thus, septin rods characterized to date contain two copies of each septin subunit assembled into a nonpolar, heteromeric complex (Fig.…”

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confidence: 99%

Septin assemblies form by diffusion-driven annealing on membranes

Bridges

Zhang

Mehta

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

172

223

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Septins assemble into filaments and higher-order structures that act as scaffolds for diverse cell functions including cytokinesis, cell polarity, and membrane remodeling. Despite their conserved role in cell organization, little is known about how septin filaments elongate and are knitted together into higher-order assemblies. Using fluorescence correlation spectroscopy, we determined that cytosolic septins are in small complexes, suggesting that septin filaments are not formed in the cytosol. When the plasma membrane of live cells is monitored by total internal reflection fluorescence microscopy, we see that septin complexes of variable size diffuse in two dimensions. Diffusing septin complexes collide and make end-on associations to form elongated filaments and higher-order structures, an assembly process we call annealing. Septin assembly by annealing can be reconstituted in vitro on supported lipid bilayers with purified septin complexes. Using the reconstitution assay, we show that septin filaments are highly flexible, grow only from free filament ends, and do not exchange subunits in the middle of filaments. This work shows that annealing is a previously unidentified intrinsic property of septins in the presence of membranes and demonstrates that cells exploit this mechanism to build large septin assemblies.cytoskeleton | biophysics S eptin filaments form rings, bars, and gauzes that serve as a scaffold at cell division sites; act to retract blebbed regions of membrane; and restrict diffusion between cell compartments (1-4). Septin function is required for cell division and viability in many eukaryotes whereas misregulation is associated with cancers and neurodegenerative disorders (5-8). Furthermore, septins mediate entry of both bacterial and fungal pathogens into host cells (9-11). In vivo, septin assembly is restricted both in time and in space through local activation of small GTPases such as Cdc42. Localized signaling leads to higher-order septin structures forming closely apposed to the plasma membrane at the plane of division, sites of polarity, and curved membranes (10,(12)(13)(14). Notably, eukaryotic cells of different geometries build higher-order septin assemblies of various shapes, sizes, and functions (4, 15, 16). Although septins are critical for spatial organization of cell plasma membranes, their assembly and disassembly dynamics are not understood (15).Electron microscopy (EM) studies of recombinant and immunoprecipitated Saccharomyces cerevisiae septins have shown that septins form nonpolar hetero-octameric rod-shaped complexes in high-salt buffers (>300 mM) and elongated filaments when dialyzed into low-salt buffers (<100 mM) (17, 18). Structural analyses of worm and mammalian septins have revealed that the heteromeric, rod-shaped complex is conserved (19-21). Thus, septin rods characterized to date contain two copies of each septin subunit assembled into a nonpolar, heteromeric complex (Fig. S1). Association of purified septin proteins with phosphoinositide-containing membrane monola...

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The Caenorhabditis elegans septin complex is nonpolar

Cited by 140 publications

References 53 publications

Heterotypic Coiled-Coil Formation is Essential for the Correct Assembly of the Septin Heterofilament

Heterotypic Coiled-Coil Formation is Essential for the Correct Assembly of the Septin Heterofilament

Cooperation Between the Septins and the Actomyosin Ring and Role of a Cell-Integrity Pathway During Cell Division in Fission Yeast

Septin assemblies form by diffusion-driven annealing on membranes

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