Wnt5a signaling promotes apical and basolateral polarization of single epithelial cells

Gon, Hidetoshi; Fumoto, Katsumi; Ku, Yonson; Matsumoto, Shinji; Kikuchi, Akira

doi:10.1091/mbc.e13-07-0357

Cited by 28 publications

(28 citation statements)

References 49 publications

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“…In keeping with the association of Wnt5a signaling with actin dynamics and organelle movements (12)(13)(14)22), we questioned whether the detrimental effect of Wnt5a on parasites internalized by macrophages could result, at least in part, from Wnt5a-induced alterations in cytoskeletal dynamics. Given that the Rac1/Rho family GTPases are Wnt5a signaling intermediates (16,17,21), we rationalized that Wnt5a-Rac1/Rho-mediated changes in the cytoskeletal actin organization and associated NOX activity (23)(24)(25)(26) could restrict the formation and sustainment of PVs crucial for parasite survival in macrophages (12)(13)(14)37).…”

Section: Wnt5a-rac1/rho Gtpase-mediated Altered Cytoskeletal Dynamicsmentioning

confidence: 98%

Wnt5a Signaling Promotes Host Defense againstLeishmania donovaniInfection

Chakraborty

Kurati

Mahata

et al. 2017

The Journal of Immunology

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Leishmania donovani infects macrophages, disrupting immune homeostasis. The underlying mechanism that sustains infection remains unresolved. In view of the potential of Wnt5a signaling to support immune homeostasis, we evaluated the interrelationship of Wnt5a signaling and Leishmania donovani infection. Upon infecting macrophages separately with antimony drug–sensitive and –resistant L. donovani, we noted disruption in the steady-state level of Wnt5a. Moreover, inhibition of Wnt5a signaling by small interfering RNA transfection in vitro or by use of inhibitor of Wnt production in vivo led to an increase in cellular parasite load. In contrast, treatment of macrophages with recombinant Wnt5a caused a decrease in the load of antimony-sensitive and -resistant parasites, thus confirming that Wnt5a signaling antagonizes L. donovani infection. Using inhibitors of the Wnt5a signaling intermediates Rac1 and Rho kinase, we demonstrated that Wnt5a-mediated inhibition of parasite infection in macrophages is Rac1/Rho dependent. Furthermore, phalloidin staining and reactive oxygen species estimation of Wnt5a-treated macrophages suggested that a Wnt5a-Rac/Rho–mediated decrease in parasite load is associated with an increase in F- actin assembly and NADPH oxidase activity. Moreover, live microscopy of L. donovani–infected macrophages treated with Wnt5a demonstrated increased endosomal/lysosomal fusions with parasite-containing vacuoles (parasitophorous vacuoles [PV]). An increase in PV–endosomal/lysosomal fusion accompanied by augmented PV degradation in Wnt5a-treated macrophages was also apparent from transmission electron microscopy of infected cells. Our results suggest that, although L. donovani evades host immune response, at least in part through inhibition of Wnt5a signaling, revamping Wnt5a signaling can inhibit L. donovani infection, irrespective of drug sensitivity or resistance.

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Section: Wnt5a-rac1/rho Gtpase-mediated Altered Cytoskeletal Dynamicsmentioning

confidence: 98%

Wnt5a Signaling Promotes Host Defense againstLeishmania donovaniInfection

Chakraborty

Kurati

Mahata

et al. 2017

The Journal of Immunology

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“…Because Wnt5a stimulation correlates with Rac1 activity (9,23,24,27), we investigated whether the homeostatic Wnt5a arbitrated basal NF-kB activity in macrophages with concurrent CD14 expression is Rac1 dependent. Initially, we confirmed that Wnt5a-depleted macrophages harbor reduced levels of basally activated Rac1 by demonstrating an ∼50% reduced level of GTP-gS bound Rac1 in the Wnt5A siRNA-transfected RAW264.7 macrophages compared with the corresponding controls (Fig.…”

Section: Wnt5a-nf-kb-cd14 Axis In Macrophages Is Rac1 Dependentmentioning

confidence: 99%

“…The cytoplasmic adapter protein disheveled (Dvl), is crucial for both b-catenin2dependent and independent Wnt5a signaling (16-18, 23, 24). Contemporary research highlights how different cellular proteins orchestrate Dvl function (23,24). However, the precise biochemical mechanisms of Dvl coupling to the steady state versus activated conformations of ligand-receptor combinations of Wnt5a-Fz/ROR in different cell types are not completely understood.…”

mentioning

confidence: 99%

Wnt5a–Rac1–NF-κB Homeostatic Circuitry Sustains Innate Immune Functions in Macrophages

Naskar

Maiti

Chakraborty

et al. 2014

The Journal of Immunology

121

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Macrophages play a critical role in innate immunity. Differentiation Ags present on macrophages such as CD14 orchestrate the first line of defense against infection. The basal/homeostatic signaling scheme that keeps macrophages thus groomed for innate immune functions remains unresolved. Wnt5a–Fz5 signaling being a primordial event during cell differentiation, we examined the involvement of Wnt5a–Fz5 signaling in the maintenance of innate immune functions. In this study, we demonstrate that innate immune functions of macrophages ensue at least partly through a homeostatic Wnt5a–Fz5–NF-κB (p65) circuit, which is Rac1 dependent. The autocrine/paracrine Wnt5a–Fz5–Rac1–p65 signaling cascade not only maintains basal levels of the immune defense modulating IFNs and CD14; it also supports macrophage survival. Wnt5a–Fz5–Rac1 signaling mediated p65 homeostasis in turn sustains Wnt5a expression in a feed-forward mode. The natural immune response of macrophages to Escherichia coli/LPS and virus is accordingly sustained. The depiction of sustenance of innate immune functions as an outcome of a homeostatic Wnt5a–p65 axis unfolds previously unidentified details of immune regulation and provides new insight into homeostatic cell signaling.

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“…The central inductive cue(s) that drives non-muscle myosin II activation during gastrulation is constituted by Wnt signaling [200,265]. This function of Wnt seems to be conserved during later development [268] and among animals: Wnt signaling can cell-autonomously modulate actomyosin distribution, activity, and apical-basal polarization [269,270], and Wnt/planar cell polarity pathway components also seem to directly modulate actin dynamics [271]. Notably, an ancestral Wnt-like system in D. discoideum is responsible for actomyosin-mediated morphogenesis [272].…”

Section: Actomyosinmentioning

confidence: 99%

Cytoskeletal Symmetry Breaking and Chirality: From Reconstituted Systems to Animal Development

Pohl

2015

Symmetry

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Animal development relies on repeated symmetry breaking, e.g., during axial specification, gastrulation, nervous system lateralization, lumen formation, or organ coiling. It is crucial that asymmetry increases during these processes, since this will generate higher morphological and functional specialization. On one hand, cue-dependent symmetry breaking is used during these processes which is the consequence of developmental signaling. On the other hand, cells isolated from developing animals also undergo symmetry breaking in the absence of signaling cues. These spontaneously arising asymmetries are not well understood. However, an ever growing body of evidence suggests that these asymmetries can originate from spontaneous symmetry breaking and self-organization of molecular assemblies into polarized entities on mesoscopic scales. Recent discoveries will be highlighted and it will be discussed how actomyosin and microtubule networks serve as common biomechanical systems with inherent abilities to drive spontaneous symmetry breaking.

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Wnt5a signaling promotes apical and basolateral polarization of single epithelial cells

Cited by 28 publications

References 49 publications

Wnt5a Signaling Promotes Host Defense againstLeishmania donovaniInfection

Wnt5a Signaling Promotes Host Defense againstLeishmania donovaniInfection

Wnt5a–Rac1–NF-κB Homeostatic Circuitry Sustains Innate Immune Functions in Macrophages

Cytoskeletal Symmetry Breaking and Chirality: From Reconstituted Systems to Animal Development

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