Novel septin 9 repeat motifs altered in neuralgic amyotrophy bind and bundle microtubules

X, Bai; Bowen, Jonathan R.; Knox, Tara K.; Zhou, Kaifeng; Pendziwiat, Manuela; Kuhlenbäumer, Gregor; Sindelar, Charles V.; Spiliotis, Elias T.

doi:10.1083/jcb.201308068

Cited by 105 publications

(150 citation statements)

References 36 publications

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“…In this manuscript we focus on SEPT9 which belongs to the SEPT3 subgroup and has a unique N-terminal domain (NTD) consisting of a basic domain (B-domain) and an acidic domain (A-domain) (Fig. 1a) 3 . All septins have a GTP-binding domain (G-domain), which is evolutionarily and structurally related to the Ras GTPases 4 .…”

Section: Introductionmentioning

confidence: 99%

Septin 9 Exhibits Polymorphic Binding to F-Actin and Inhibits Myosin and Cofilin Activity

Smith

Dolat

Angelis

et al. 2015

Journal of Molecular Biology

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Septins are a highly conserved family of proteins in eukaryotes that is recognized as a novel component of the cytoskeleton. Septin 9 (SEPT9) interacts directly with actin filaments and functions as an actin stress fiber cross-linking protein that promotes the maturation of nascent focal adhesions and cell migration. However, the molecular details of how SEPT9 interacts with F-actin remain unknown. Here, we use electron microscopy and image analysis to show that SEPT9 binds to F-actin in a highly polymorphic fashion. We demonstrate that the basic domain (B-domain) of the N-terminal tail of SEPT9 is responsible for actin cross-linking, while the GTP-binding domain (G-domain) does not bundle F-actin. We show that the B-domain of SEPT9 binds to three sites on F-actin, and the two of these sites overlap with the binding regions of myosin and cofilin. SEPT9 inhibits actin-dependent ATPase activity of myosin and competes with the weakly-bound state of myosin for binding to F-actin. At the same time, SEPT9 significantly reduces the extent of F-actin depolymerization by cofilin. Taken together, these data suggest that SEPT9 protects actin filaments from depolymerization by cofilin and myosin, and indicate a mechanism by which SEPT9 could maintain the integrity of growing and contracting actin filaments.

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Section: Introductionmentioning

confidence: 99%

Septin 9 Exhibits Polymorphic Binding to F-Actin and Inhibits Myosin and Cofilin Activity

Smith

Dolat

Angelis

et al. 2015

Journal of Molecular Biology

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“…SEPT9 associates with microtubules and mediates their crosslinking into bundles due to electrostatic interactions between its N-terminus and the C-terminus of β-tubulin [124]. The N-terminal part of SEPT9 contains several repeats of two motifs, K/R-x-x-E/D and R/K-R-x-E, which were found to be critically important for the SEPT9 effect on microtubules in vitro.…”

Section: Interactions With Actin and Microtubulesmentioning

confidence: 99%

“…This result was also confirmed in vivo in MDCK cells. It was shown that SEPT9-dependent formation of microtubule bundles is extremely important for correct axon growth [124]. For other septins, the mechanisms of their binding to microtubules are currently unknown.…”

Section: Interactions With Actin and Microtubulesmentioning

confidence: 99%

СЕПТИНОВЫЕ КОМПЛЕКСЫ И?ДИНАМИКА ЦИТОСКЕЛЕТА, "Молекулярная Биология"

Akhmetova¹,

Chesnokov²,

Федорова³

2018

Молекулярная биология

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Septins belong to a family of conserved GTP-binding proteins found in majority of eukaryotic species except for higher plants. Septins form nonpolar complexes that further polymerize into filaments and associate with cell membranes, thus comprising newly acknowledged cytoskeletal system. Septins participate in a variety of cell processes and contribute to various pathophysiological states, including tumorigenesis and neurodegeneration. Here, we review the structural and functional properties of septins and the regulation of their dynamics with special emphasis on the role of septin filaments as a cytoskeletal system and its interaction with actin and microtubule cytoskeletons. We also discuss how septins compartmentalize the cell by forming local protein-anchoring scaffolds and by providing barriers for the lateral diffusion of the membrane proteins.

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“…Interestingly, Um Sep4 (a Cdc10 ortholog), the only septin protein lacking a C-terminal coiled-coil domain, forms fibers running along the length of the cell that partially co-localize with microtubules yet do not depend on microtubules for localization (Figure 1b) [30]. Notably, mammalian septins have been found to associate with microtubules and microtubule associated proteins [32,33]. Do examples of independent septin localizations imply separable functions for individual septins?…”

Section: How Do Septin Localizations and Dynamics Vary In Different Pmentioning

confidence: 99%

Fungal pathogens are platforms for discovering novel and conserved septin properties

Bridges

Gladfelter

2014

Current Opinion in Microbiology

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Septins are filament-forming GTP-binding proteins that act as scaffolds in diverse cell functions including division, polarity and membrane remodeling. In a variety of fungal pathogens, it has been observed that septins are required for virulence because cells are unable to survive or are misshapen when septins are mutated. Cell morphology is interconnected with pathogenesis and thus septin mutants displaying aberrant cell morphologies are commonly deficient in host tissue invasion. The degree to which septins orchestrate versus maintain changes in fungal cell morphology during pathogenesis remains to be determined. Aside from the importance of septins in the process of pathogenesis, animal and plant fungal pathogens display complexity in septin form, dynamics, and function not seen in S. cerevisiae making these organisms important models for uncovering diversity in septin behavior. Additionally, host septins have recently been implicated in the process of C. albicans invasion, motivating the need to examine host septins in fungal pathogenesis. Understanding the role of septins in the host-pathogen interaction not only illuminates pathogenesis mechanisms but importantly also expands our understanding of septin biology in general.

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Novel septin 9 repeat motifs altered in neuralgic amyotrophy bind and bundle microtubules

Abstract: Novel septin 9 repeat motifs interact with the acidic C-terminal tails of β-tubulin to promote microtubule bundling and asymmetric neurite growth.

Cited by 105 publications

References 36 publications

Septin 9 Exhibits Polymorphic Binding to F-Actin and Inhibits Myosin and Cofilin Activity

Septin 9 Exhibits Polymorphic Binding to F-Actin and Inhibits Myosin and Cofilin Activity

СЕПТИНОВЫЕ КОМПЛЕКСЫ И?ДИНАМИКА ЦИТОСКЕЛЕТА, "Молекулярная Биология"

Fungal pathogens are platforms for discovering novel and conserved septin properties

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