PLEKHG3 enhances polarized cell migration by activating actin filaments at the cell front

Nguyen, Trang; Park, Wei Sun; Park, Byung Ouk; Kim, Cha Yeon; Oh, Yohan; Kim, Jin Man; Choi, Heechul; Kyung, Taeyoon; Kim, Cheol-Hee; Lee, Gabsang; Hahn, Klaus M.; Meyer, Tobias; Heo, Won Do

doi:10.1073/pnas.1604720113

Cited by 33 publications

(45 citation statements)

References 44 publications

(51 reference statements)

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“…On the opposite side of the cell, ruffling was inhibited and membrane retraction was observed. Repeated activation of opto-Dab1 induced cell migration, similar to that observed with optically activated Rac1 and PLEKHG33738. These results suggest that local activation of Dab1 can induce polarization of intracellular signals and morphological asymmetry.…”

Section: Discussionsupporting

confidence: 76%

Optogenetic control of the Dab1 signaling pathway

Wang

Cooper

2017

Sci Rep

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The Reelin-Dab1 signaling pathway regulates development of the mammalian brain, including neuron migrations in various brain regions, as well as learning and memory in adults. Extracellular Reelin binds to cell surface receptors and activates phosphorylation of the intracellular Dab1 protein. Dab1 is required for most effects of Reelin, but Dab1-independent pathways may contribute. Here we developed a single-component, photoactivatable Dab1 (opto-Dab1) by using the blue light-sensitive dimerization/oligomerization property of A. thaliana Cryptochrome 2 (Cry2). Opto-Dab1 can activate downstream signals rapidly, locally, and reversibly upon blue light illumination. The high spatiotemporal resolution of the opto-Dab1 probe also allows us to control membrane protrusion, retraction and ruffling by local illumination in both COS7 cells and in primary neurons. This shows that Dab1 activation is sufficient to orient cell movement in the absence of other signals. Opto-Dab1 may be useful to study the biological functions of the Reelin-Dab1 signaling pathway both in vitro and in vivo.

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Section: Discussionsupporting

confidence: 76%

Optogenetic control of the Dab1 signaling pathway

Wang

Cooper

2017

Sci Rep

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“…Rho-family GTPases act as molecular switches by cycling between inactive GDP and active GTP-bound states of GTPases to regulate the activity of F-actin and are critical for the stimulation of cell migration in response to various stresses (53). In humans, there are Ͼ20 members of the Rho family, but the relative contribution of each Rho GTPase depends on the environment and cell type (54,55). The role of three GTPases, Cdc42, Rac1, and RhoA, in the coordination of the actin cytoskeleton has been extensively investigated in different cell types, including IECs.…”

Section: Discussionmentioning

confidence: 99%

HuR Enhances Early Restitution of the Intestinal Epithelium by Increasing Cdc42 Translation

Liu

Zhuang

Xiao

et al. 2017

Molecular and Cellular Biology

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The mammalian intestinal mucosa exhibits a spectrum of responses after acute injury and repairs itself rapidly to restore the epithelial integrity. The RNAbinding protein HuR regulates the stability and translation of target mRNAs and is involved in many aspects of gut epithelium homeostasis, but its exact role in the regulation of mucosal repair after injury remains unknown. We show here that HuR is essential for early intestinal epithelial restitution by increasing the expression of cell division control protein 42 (Cdc42) at the posttranscriptional level. HuR bound to the Cdc42 mRNA via its 3= untranslated region, and this association specifically enhanced Cdc42 translation without an effect on the Cdc42 mRNA level. Intestinal epithelium-specific HuR knockout not only decreased Cdc42 levels in mucosal tissues, but it also inhibited repair of damaged mucosa induced by mesenteric ischemia/reperfusion in the small intestine and by dextran sulfate sodium in the colon. Furthermore, Cdc42 silencing prevented HuR-mediated stimulation of cell migration over the wounded area by altering the subcellular distribution of F-actin. These results indicate that HuR promotes early intestinal mucosal repair after injury by increasing Cdc42 translation and demonstrate the importance of HuR deficiency in the pathogenesis of delayed mucosal healing in certain pathological conditions.

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“…Moreover, PLEKHG3 is regulated by phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). However, it is currently unknown which PI3K isoforms are responsible for PLEKHG3 activation [9]. …”

Section: Roles Of Dynamic Actin Cytoskeleton and Actin-associated Promentioning

confidence: 99%

The roles and regulation of the actin cytoskeleton, intermediate filaments and microtubules in smooth muscle cell migration

2017

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Smooth muscle cell migration has been implicated in the development of respiratory and cardiovascular systems; and airway/vascular remodeling. Cell migration is a polarized cellular process involving a protrusive cell front and a retracting trailing rear. There are three cytoskeletal systems in mammalian cells: the actin cytoskeleton, the intermediate filament network, and microtubules; all of which regulate all or part of the migrated process. The dynamic actin cytoskeleton spatially and temporally regulates protrusion, adhesions, contraction, and retraction from the cell front to the rear. c-Abl tyrosine kinase plays a critical role in regulating actin dynamics and migration of airway smooth muscle cells and nonmuscle cells. Recent studies suggest that intermediate filaments undergo reorganization during migration, which coordinates focal adhesion dynamics, cell contraction, and nucleus rigidity. In particular, vimentin intermediate filaments undergo phosphorylation and reorientation in smooth muscle cells, which may regulate cell contraction and focal adhesion assembly/disassembly. Motile cells are characterized by a front-rear polarization of the microtubule framework, which regulates all essential processes leading to cell migration through its role in cell mechanics, intracellular trafficking, and signaling. This review recapitulates our current knowledge how the three cytoskeletal systems spatially and temporally modulate the migratory properties of cells. We also summarize the potential role of migration-associated biomolecules in lung and vascular diseases.

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PLEKHG3 enhances polarized cell migration by activating actin filaments at the cell front

Cited by 33 publications

References 44 publications

Optogenetic control of the Dab1 signaling pathway

Optogenetic control of the Dab1 signaling pathway

HuR Enhances Early Restitution of the Intestinal Epithelium by Increasing Cdc42 Translation

The roles and regulation of the actin cytoskeleton, intermediate filaments and microtubules in smooth muscle cell migration

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