Requirement for Pak3 in Rac1‐induced organization of actin and myosin during <i>Drosophila</i> larval wound healing

Baek, Seung Hee; Cho, Hae Weon; Kwon, Yumi; Lee, Ji Hyun; Kim, Moon Jong; Lee, Hyangkyu; Choe, Kwang Min

doi:10.1016/j.febslet.2012.01.061

Cited by 24 publications

(29 citation statements)

References 39 publications

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“…Based on our analysis combined with previous findings (Baek et al, 2012;Duan et al, 2012), we propose that Pak3 functions downstream of Rac GTPase in guidance receptor signaling to modulate efficient border cell movement. In Pak3-compromised border cells, the distribution of polarity proteins is significantly altered.…”

Section: Discussionsupporting

confidence: 64%

“…flies (Duan et al, 2012;Baek et al, 2012). Since depletion of Pak3 or guidance receptor function affects the apical-basal polarity of migrating border cells, we proposed that if Rac GTPase functions in the same biochemical pathway as Pak3 then it should also affect the apical-basal polarity of the migrating cluster.…”

Section: Rac1 Mediates Apical-basal Polarity In Moving Border Cellsmentioning

confidence: 97%

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dPak3 regulates apical-basal polarity in migrating border cells during Drosophila oogenesis

et al. 2015

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Group cell migration is a highly coordinated process that is involved in a number of physiological events such as morphogenesis, wound healing and tumor metastasis. Unlike single cells, collectively moving cells are physically attached to each other and retain some degree of apical-basal polarity during the migratory phase. Although much is known about direction sensing, how polarity is regulated in multicellular movement remains unclear. Here we report the role of the protein kinase Pak3 in maintaining apical-basal polarity in migrating border cell clusters during Drosophila oogenesis. Pak3 is enriched in border cells and downregulation of its function impedes border cell movement. Time-lapse imaging suggests that Pak3 affects protrusive behavior of the border cell cluster, specifically regulating the stability and directionality of protrusions. Pak3 functions downstream of guidance receptor signaling to regulate the level and distribution of F-actin in migrating border cells. We also provide evidence that Pak3 genetically interacts with the lateral polarity marker Scribble and that it regulates JNK signaling in the moving border cells. Since Pak3 depletion results in mislocalization of several apical-basal polarity markers and overexpression of Jra rescues the polarity of the Pak3-depleted cluster, we propose that Pak3 functions through JNK signaling to modulate apical-basal polarity of the migrating border cell cluster. We also observe loss of apical-basal polarity in Rac1-depleted border cell clusters, suggesting that guidance receptor signaling functions through Rac GTPase and Pak3 to regulate the overall polarity of the cluster and mediate efficient collective movement of the border cells to the oocyte boundary.

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Section: Discussionsupporting

confidence: 64%

Section: Rac1 Mediates Apical-basal Polarity In Moving Border Cellsmentioning

confidence: 97%

dPak3 regulates apical-basal polarity in migrating border cells during Drosophila oogenesis

et al. 2015

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“…Changes in cell morphology are often caused by cytoskeletal rearrangement and PAK3 has been shown to be essential for the organization of F-actin at the leading edge of submarginal cells [27]. We investigated whether the morphological changes associated with PAK3 inhibition were linked to changes in actin re-distribution.…”

Section: Resultsmentioning

confidence: 99%

“…CDC42 is thought to activate fillopodia formation, while the three isoforms of Rac (1, 2, 3) regulate actin polymerization at the periphery of the cell and control the development of membrane ruffles and lamellipodia [32]–[34]. Though the role of PAK proteins in these actin remodeling functions of CDC42 and Rac, PAK3, in particular, has been shown to be essential for the organization of F-actin at the leading edge of submarginal cells [27]. In this study we show a role for PAK3 in the altered morphology of AP-1 transformed cells and actin reorganization underlying these morphological changes.…”

Section: Discussionmentioning

confidence: 99%

p21-Activated Kinase 3 (PAK3) Is an AP-1 Regulated Gene Contributing to Actin Organisation and Migration of Transformed Fibroblasts

et al. 2013

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Activating Protein 1 (AP-1) plays a vital role in cell proliferation, differentiation and apoptosis. While de-regulation of AP-1 has been linked to many cancers, little is known regarding its downstream transcriptional targets that associate with cellular transformation. Previous studies identified PAK3, a serine/threonine kinase, as a potential AP-1 target gene. PAK3 has been implicated in a variety of pathological disorders and over-expression of other PAK-family members has been linked to cancer. In this study, we investigate AP-1 regulation of PAK3 expression and the role of PAK3 in cJun/AP-1-associated cellular transformation. Our results showed elevated PAK3 expression at both the mRNA and protein level in cJun-over-expressing Rat1a fibroblasts, as well as in transformed human fibroblasts. Elevated PAK3 expression in cJun/AP-1 over-expressing cells associated with a significant increase in PAK3 promoter activation. This increased promoter activity was lost when a single putative Jun binding site, which can bind AP-1 directly both in vitro and in vivo, was mutated. Further, inhibition of PAK3 using siRNA showed a regression in the cell morphology, migratory potential and actin organisation associated with AP-1 transformed cells. Our study is a first to describe a role for AP-1 in regulating PAK3 expression and suggest that PAK3 is an AP-1 target required for actin organization and migration observed in transformed cells.

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“…We next considered the opposite argument, namely that the excessive cell fusion in JAK/STAT-deficient larvae might be a consequence of defects in cell shape change; we thought this case unlikely. Larvae with defects in wound closure, including those deficient in JNK, Pak3 or non-muscle myosin II, do not generally display excessive cell fusion during wound healing (Galko and Krasnow, 2004;Kwon et al, 2010;Baek et al, 2012).…”

Section: Cell Proliferation or Apoptosis Was Not Involved In Excess Cmentioning

confidence: 99%

Spatiotemporal regulation of cell fusion by JNK and JAK/STAT signaling during Drosophila wound healing

Lee¹,

Lee²,

Park³

et al. 2017

Development

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Cell-cell fusion is widely observed during development and disease, and imposes a dramatic change on participating cells. Cell fusion should be tightly controlled, but the underlying mechanism is poorly understood. Here, we found that the JAK/STAT pathway suppressed cell fusion during wound healing in the Drosophila larval epidermis, restricting cell fusion to the vicinity of the wound. In the absence of JAK/STAT signaling, a large syncytium containing a 3-fold higher number of nuclei than observed in wild-type tissue formed in wounded epidermis. The JAK/STAT ligand-encoding genes upd2 and upd3 were transcriptionally induced by wounding, and were required for suppressing excess cell fusion. JNK (also known as Basket in flies) was activated in the wound vicinity and activity peaked at ∼8 h after injury, whereas JAK/STAT signaling was activated in an adjoining concentric ring and activity peaked at a later stage. Cell fusion occurred primarily in the wound vicinity, where JAK/STAT activation was suppressed by fusion-inducing JNK signaling. JAK/ STAT signaling was both necessary and sufficient for the induction of βPS integrin (also known as Myospheroid) expression, suggesting that the suppression of cell fusion was mediated at least in part by integrin protein.

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Requirement for Pak3 in Rac1‐induced organization of actin and myosin during Drosophila larval wound healing

Cited by 24 publications

References 39 publications

dPak3 regulates apical-basal polarity in migrating border cells during Drosophila oogenesis

dPak3 regulates apical-basal polarity in migrating border cells during Drosophila oogenesis

p21-Activated Kinase 3 (PAK3) Is an AP-1 Regulated Gene Contributing to Actin Organisation and Migration of Transformed Fibroblasts

Spatiotemporal regulation of cell fusion by JNK and JAK/STAT signaling during Drosophila wound healing

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