Rho-Kinase and Myosin-II Control Phagocytic Cup Formation during CR, but Not FcγR, Phagocytosis

Olazabal, Isabel M.; Caron, Emmanuelle; May, Robin C.; Schilling, Kerstin; Knecht, David A.; Machesky, Laura M.

doi:10.1016/s0960-9822(02)01069-2

Cited by 226 publications

(224 citation statements)

References 29 publications

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“…The fact that Rac1 activity is not required for this uptake mechanism provides further support for our conclusion. 33 To confirm further the involvement of distinct signaling pathways involving phagocytosis and fusion, we observed that MCP-1-null macrophages, which are inherently deficient in fusion, displayed normal engulfment of microspheres.…”

Section: Inhibition Of Fbgc Formation In Vivo By Prolonged Release Ofmentioning

confidence: 85%

Foreign Body Giant Cell Formation Is Preceded by Lamellipodia Formation and Can Be Attenuated by Inhibition of Rac1 Activation

Jay

Skokos

Laiwalla

et al. 2007

The American Journal of Pathology

105

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Macrophages that are recruited to the site of implanted biomaterials undergo fusion to form surfacedamaging foreign body giant cells. Exposure of peripheral blood monocytes to interleukin-4 can recapitulate the fusion process in vitro. In this study, we used interleukin-4 to induce multinucleation of murine bone marrow-derived macrophages and observed changes in cell shape, including elongation and lamellipodia formation, before fusion. Because cytoskeletal rearrangements are regulated by small GTPases, we examined the effects of inhibitors of Rho kinase (Y-32885) and Rac activation (NSC23766) on fusion. Y-32885 did not prevent cytoskeletal changes or fusion but limited the extent of multinucleation. NSC23766, on the other hand, inhibited lamellipodia formation and fusion in a dose-dependent manner. In addition, we found that in control cells, these changes were preceded by Rac1 activation. However, NSC23766 did not block the uptake of polystyrene microspheres. Likewise, short interfering RNA knockdown of Rac1 limited fusion without limiting phagocytosis. Thus, phagocytosis and fusion can be partially decoupled based on their susceptibility to NSC23766. Furthermore, poly(ethylene-co-vinyl acetate) scaffolds containing NSC23766 attenuated foreign body giant cell formation in vivo. These observations suggest that targeting Rac1 activation could protect biomaterials without compromising the ability of macrophages to perform beneficial phagocytic functions at implantation sites. (Am J Pathol

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Section: Inhibition Of Fbgc Formation In Vivo By Prolonged Release Ofmentioning

confidence: 85%

Foreign Body Giant Cell Formation Is Preceded by Lamellipodia Formation and Can Be Attenuated by Inhibition of Rac1 Activation

Jay

Skokos

Laiwalla

et al. 2007

The American Journal of Pathology

105

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“…Phagocytosis involves the active protrusion of lamellipodia around an object that is to be engulfed, and several myosin classes are involved in this process. Myosin Ic 9 and myosin X 10 seem to be key players in the extension of phagocytic cup pseudopods, whereas myosin II promotes closure of the cup 11 (FIG. 2).…”

Section: Processivitymentioning

confidence: 99%

Powering membrane traffic in endocytosis and recycling

Soldati

Schliwa

2006

Nat Rev Mol Cell Biol

314

279

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| Early in evolution, the diversification of membrane-bound compartments that characterize eukaryotic cells was accompanied by the elaboration of molecular machineries that mediate intercompartmental communication and deliver materials to specific destinations. Molecular motors that move on tracks of actin filaments or microtubules mediate the movement of organelles and transport between compartments. The subjects of this review are the motors that power the transport steps along the endocytic and recycling pathways, their modes of attachment to cargo and their regulation.The emergence of eukaryotic cells was accompanied by the development of endomembrane systems that compartmentalize biochemical pathways and biosynthetic processes. An evolutionary trend towards increasing complexity and subcellular specialization necessitated the development of machineries for intercompartmental communication. Molecular assemblies evolved to confer specificity to the interactions of donor and acceptor compartments (budding, sorting, tethering and fusion). Cytoskeletal polymers such as actin filaments and microtubules, which help segregate genetic material and determine cell shape and subcellular architecture, were co-opted as tracks for transport. In animal cells, microtubules support long-range transport, whereas the more flexible actin filaments serve short-range movements both near the cell periphery and in the cell interior. Also, actin filaments can be woven into dense networks of short fibres through the action of crosslinkers and branchpromoting complexes. On the other hand, in many plant cells, bundled actin filaments can form extended tracks for long-distance transport. Owing to the gel-like nature of the cytoplasm, the Brownian movement of organelles is severely restricted and cargoes have to be transported to their destinations at the expense of energy. Furthermore, seemingly random, but motor-dependent, movement is proposed to increase the probability of vesicle collisions and therefore promote fusion events. Movement is powered by three ATP-dependent motors: myosin, kinesin and dynein. Over the course of eukaryotic evolution, these motors have diversified into a large number of families with specific tasks (FIG. 1).Here, we review the involvement of molecular motors in the movement of endosomes and in vesicular trafficking along the endocytic and recycling pathways. These pathways are summarized in FIG. 2. We do not, however,

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“…The negative effect of Rho/ROCK during engulfment of apoptotic cells differs from other types of phagocytosis mediated via the complement receptor and Fc receptor, respectively. Rho and ROCK have been shown to be critical for complement receptor-mediated phagocytosis, and but not for Fc receptor-mediated phagocytosis [12,100]. Recently, ROCk2 activity, but not ROCK1 activity, has been shown to facilitate phagocytic uptake of fibronectin-coated beads [151].…”

Section: Phagocytosis Of Apoptotic Cellsmentioning

confidence: 99%

Rho kinase in the regulation of cell death and survival

Shi

Wei

2007

Arch. Immunol. Ther. Exp.

219

183

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SummaryRho kinase (ROCK) belongs to a family of serine/threonine kinases that are activated via interaction with Rho GTPases. ROCK is involved in a wide range of fundamental cellular functions such as contraction, adhesion, migration, and proliferation. Recent studies have shown that ROCK plays an important role in the regulation of apoptosis in various cell types and animal disease models. Two ROCK isoforms, ROCK1 and ROCK2, are assumed to be function redundant, based largely on kinase construct overexpression, and chemical inhibitors (Y27632 and fasudil), which inhibit both ROCK1 and ROCK2. Gene targeting and RNA interference approaches allow further dissection of distinct cellular, physiological and patho-physiological functions of the two ROCK isoforms. This review, based on recent molecular, cellular and animal studies, focuses on the current understanding of ROCK signaling in the regulation of apoptosis and highlights the new findings from recently generated ROCK-deficient mice.

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Rho-Kinase and Myosin-II Control Phagocytic Cup Formation during CR, but Not FcγR, Phagocytosis

Cited by 226 publications

References 29 publications

Foreign Body Giant Cell Formation Is Preceded by Lamellipodia Formation and Can Be Attenuated by Inhibition of Rac1 Activation

Foreign Body Giant Cell Formation Is Preceded by Lamellipodia Formation and Can Be Attenuated by Inhibition of Rac1 Activation

Powering membrane traffic in endocytosis and recycling

Rho kinase in the regulation of cell death and survival

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