The unusual dynamics of parasite actin result from isodesmic polymerization

Skillman, Kristen M.; Christopher, I.; Fremont, Daved H.; Diraviyam, Karthikeyan; Cooper, John A.; Sept, David; Sibley, L. David

doi:10.1038/ncomms3285

Cited by 65 publications

(95 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mixed (i.e., isodesmic and cooperative) modes of assembly have been speculated to exist for FtsZ and even actin displays isodesmic or nucleation-elongation assembly kinetics depending on the species of origin (33,34). For example, animal F-actin assembly clearly displays a nucleation-elongation mechanism of assembly, whereas parasite F-actin forms by an isodesmic process reminiscent of what we see with septins on membranes (35).…”

Section: Discussionmentioning

confidence: 96%

Septin assemblies form by diffusion-driven annealing on membranes

Bridges

Zhang

Mehta

et al. 2014

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

172

223

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionmentioning

confidence: 96%

Septin assemblies form by diffusion-driven annealing on membranes

Bridges

Zhang

Mehta

et al. 2014

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

172

223

View full text Add to dashboard Cite

show abstract

“…Therefore, parasite actin is maintained as a heterogeneous mixture of sequestered actin monomers and dynamic filaments of variable length that might originate from unusual polymerization dynamics. In contrast to the classical nucleation-elongation model (in which a critical concentration is reached before a rapid polymerization phase), the polymerization of TgACT1 in vitro and in the apparent absence of nucleators is slow, has no lag phase and increases proportionally to the number of actin molecules 35 . This accommodates an isodesmic polymerization model, in which each monomer has the same assembly and/or disassembly rate in the polymer.…”

Section: Gregarinamentioning

confidence: 90%

Gliding motility powers invasion and egress in Apicomplexa

et al. 2017

View full text Add to dashboard Cite

| Protozoan parasites have developed elaborate motility systems that facilitate infection and dissemination. For example, amoebae use actin-rich membrane extensions called pseudopodia, whereas Kinetoplastida are propelled by microtubule-containing flagella. By contrast, the motile and invasive stages of the Apicomplexa -a phylum that contains the important human pathogens Plasmodium falciparum (which causes malaria) and Toxoplasma gondii (which causes toxoplasmosis) -have a unique machinery called the glideosome, which is composed of an actomyosin system that underlies the plasma membrane. The glideosome promotes substrate-dependent gliding motility, which powers migration across biological barriers, as well as active host cell entry and egress from infected cells. In this Review, we discuss the discovery of the principles that govern gliding motility, the characterization of the molecular machinery involved, and its impact on parasite invasion and egress from infected cells. NATURE REVIEWS | MICROBIOLOGYADVANCE ONLINE PUBLICATION | 1 REVIEWS © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . ToxoplasmosisA food-borne infection caused by the parasite Toxoplasma gondii. The infection is usually mild or even asymptomatic, but can have serious consequences in patients who are immunocompromised and for the fetus in the case of primary infection during pregnancy. SporozoitesThe infectious and motile stage produced in oocysts and transmitted by the definitive host. TachyzoitesThe motile and fast-replicative stage of Toxoplasma gondii that is able to invade any nucleated cell in the host. MerozoitesThe stage of Plasmodium spp. that infects erythrocytes, in which it initiates a new asexual life cycle. Actomyosin systemA complex that comprises actin filaments, myosin and associated proteins, and that is involved in movement. GlideosomeA molecular complex that powers gliding motility in apicomplexan parasites.motility, invasion and egress. In this Review, we focus primarily on the T. gondii tachyzoite, for which functional studies were first carried out, and we compare and contrast this with the motile stages of malaria parasites -the sporozoite, merozoite and ookinete.Emergence of the capping model The motility of Apicomplexa (historically named Sporozoa) has caught the attention of scientists for more than a century 8 and was named gliding motility early on, on the basis of microscopic observations Nature Reviews | Microbiology www.nature.com/nrmicro © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . of live specimens (FIG. 2; Supplementary information S1-S5 (movies)). This mode of motility differs substantially to amoeboid motion involving pseudopods, and from the ciliary and flagellar motion used by most unicellular organisms. The main hypothesis to explain gliding motility in the early days was slime secretion, as seen in slugs; ...

show abstract

“…Also these actins can have very different characteristics compared to eukaryotic and bacterial actins. As one peculiar example, T. gondii actin exhibits isodesmic polymerization without critical concentration and nucleation phase (Skillman et al, 2013). In conclusion, it seems that ADF/cofilins are evolutionary adapted to the special features of the actin cytoskeleton in different organisms.…”

Section: Inhibition or Stimulation Of The Nucleotide Exchange Rate Ofmentioning

confidence: 99%

“…It is established that actins from lower eukaryotes, such as the Apicomplexan parasites, have very low inherent stability, which is required for the effective adaptation for gliding motility (Dobrowolski et al, 1997;Hirono et al, 1989;Sahoo et al, 2006;Schüler et al, 2005b;Skillman et al, 2011;Skillman et al, 2013). Also these actins can have very different characteristics compared to eukaryotic and bacterial actins.…”

Section: Inhibition or Stimulation Of The Nucleotide Exchange Rate Ofmentioning

confidence: 99%

The other side of the coin: Functional and structural versatility of ADF/cofilins

Hild

Kalmár

Kardos

et al. 2014

European Journal of Cell Biology

View full text Add to dashboard Cite

Several cellular processes rely on the fine tuning of actin cytoskeleton. A central component in the regulation of this cellular machinery is the ADF-H domain proteins. Despite sharing the same domain, ADF-H domain proteins produce a diverse functional landscape in the regulation of the actin cytoskeleton. Recent findings emphasize that the functional and structural features of these proteins can differ not only between ADF-H families but even within the same family. The structural and evolutional background of this functional diversity is poorly understood. This review focuses on the specific functional characteristics of ADF-H domain proteins and how these features can be linked to structural differences in the ADF-H domain and also to different conformational transitions in actin. In the light of recent discoveries we pay special attention to the ADF/cofilin proteins to find tendencies along which the functional and structural diversification is governed through the evolution.

show abstract

The unusual dynamics of parasite actin result from isodesmic polymerization

Cited by 65 publications

References 41 publications

Septin assemblies form by diffusion-driven annealing on membranes

Septin assemblies form by diffusion-driven annealing on membranes

Gliding motility powers invasion and egress in Apicomplexa

The other side of the coin: Functional and structural versatility of ADF/cofilins

Contact Info

Product

Resources

About