Choosing orientation: influence of cargo geometry and ActA polarization on actin comet tails

Lacayo, Catherine I.; Soneral, Paula A. G.; Zhu, Jie; Tsuchida, Mark A.; Footer, Matthew J.; Soo, Frederick S.; Yu, Lu; Xia, Younan; Mogilner, Alex; Theriot, Julie A.

doi:10.1091/mbc.e11-06-0584

Cited by 19 publications

(26 citation statements)

References 54 publications

(108 reference statements)

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“…As described in the Introduction, all six SH3 adapters have been implicated in cellular N-WASP activation and have been shown to bind the N-WASP proline-rich region. Because N-WASP-mediated actin assembly occurs on the cytosolic surface of cellular membranes, we used lipid bilayers supported on silica microspheres (7,35,36 (Fig. 1B).…”

Section: Resultsmentioning

confidence: 99%

Allosteric N-WASP activation by an inter-SH3 domain linker in Nck

Okrut

Prakash

et al. 2015

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

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Actin filament networks assemble on cellular membranes in response to signals that locally activate neural Wiskott-Aldrich-syndrome protein (N-WASP) and the Arp2/3 complex. An inactive conformation of N-WASP is stabilized by intramolecular contacts between the GTPase binding domain (GBD) and the C helix of the verprolin-homology, connector-helix, acidic motif (VCA) segment. Multiple SH3 domaincontaining adapter proteins can bind and possibly activate N-WASP, but it remains unclear how such binding events relieve autoinhibition to unmask the VCA segment and activate the Arp2/3 complex. Here, we have used purified components to reconstitute a signaling cascade driven by membrane-localized Src homology 3 (SH3) adapters and N-WASP, resulting in the assembly of dynamic actin networks. Among six SH3 adapters tested, Nck was the most potent activator of N-WASP-driven actin assembly. We identify within Nck a previously unrecognized activation motif in a linker between the first two SH3 domains. This linker sequence, reminiscent of bacterial virulence factors, directly engages the N-WASP GBD and competes with VCA binding. Our results suggest that animals, like pathogenic bacteria, have evolved peptide motifs that allosterically activate N-WASP, leading to localized actin nucleation on cellular membranes.

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Section: Resultsmentioning

confidence: 99%

Allosteric N-WASP activation by an inter-SH3 domain linker in Nck

Okrut

Prakash

et al. 2015

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

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“…This multi-step mechanism has been proposed to explain the slow polarization of the surface protein ActA of the Gram-positive pathogen Listeria monocytogenes (Rafelski and Theriot, 2006). When this pathogen is inside mammalian cells, ActA induces the polymerization of host actin at the cell pole, resulting in a comet actin tail that propels the bacterium inside the host cell and into neighboring cells (Kocks et al, 1992;Kocks et al, 1993;Lacayo et al, 2012). The prevailing model suggests that upon entry of the pathogen into a host cell, ActA is secreted at discrete spots along the bacterium membrane, then associates with the peptidoglycan (García-del Portillo et al, 2011) and eventually spreads uniformly along the entire cell length as a result of protein accumulation and cell wall growth.…”

Section: Growth-dependent Transmission From the Sidewallmentioning

confidence: 99%

How do bacteria localize proteins to the cell pole?

Laloux

Jacobs‐Wagner

2014

Journal of Cell Science

157

158

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It is now well appreciated that bacterial cells are highly organized, which is far from the initial concept that they are merely bags of randomly distributed macromolecules and chemicals. Central to their spatial organization is the precise positioning of certain proteins in subcellular domains of the cell. In particular, the cell poles -the ends of rod-shaped cells -constitute important platforms for cellular regulation that underlie processes as essential as cell cycle progression, cellular differentiation, virulence, chemotaxis and growth of appendages. Thus, understanding how the polar localization of specific proteins is achieved and regulated is a crucial question in bacterial cell biology. Often, polarly localized proteins are recruited to the poles through their interaction with other proteins or protein complexes that were already located there, in a so-called diffusion-and-capture mechanism. Bacteria are also starting to reveal their secrets on how the initial pole 'recognition' can occur and how this event can be regulated to generate dynamic, reproducible patterns in time (for example, during the cell cycle) and space (for example, at a specific cell pole). Here, we review the major mechanisms that have been described in the literature, with an emphasis on the self-organizing principles. We also present regulation strategies adopted by bacterial cells to obtain complex spatiotemporal patterns of protein localization.

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“…Asymmetric localization of ActA is critical for the directional movement. Using ActA-coated beads approximating the size and geometrical shape of Listeria (1.8 mm long Â 0.8 mm wide, on average), the Theriot lab recently demonstrated that polar ActA distribution allowed ellipsoidal beads to recapitulate in vitro the predominant orientation and curved trajectories observed in motile L. monocytogenes in eukaryotic cells [56 ].…”

Section: Current Opinion In Microbiologymentioning

confidence: 99%