An ELMO2-RhoG-ILK network modulates microtubule dynamics

Jackson, Bradley C.; Ivanova, Iordanka A.; Dagnino, Lina

doi:10.1091/mbc.e14-10-1444

Cited by 23 publications

(27 citation statements)

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“…The movement of E-cadherin to the cell membrane in response to Ca 2þ o requires an intact microtubule network (Jackson et al, 2015). Cortical microtubules also engage adherens and tight junctions, contributing to the establishment of epidermal barrier functions (Sumigray et al, 2012).…”

Section: Role Of Microtubules In Ca 2d -Induced Casr Membrane Translomentioning

confidence: 99%

“…Cortical microtubules also engage adherens and tight junctions, contributing to the establishment of epidermal barrier functions (Sumigray et al, 2012). Significantly, ILK is necessary for microtubule stability in keratinocytes, and its absence precludes E-cadherin trafficking to the membrane and adherens junction assembly through mechanisms that involve GSK-3b, CRMP2, and Rac1 activation (Jackson et al, 2015). Hence, we next determined if CaSR movements to the plasma membrane require intact microtubules.…”

Section: Role Of Microtubules In Ca 2d -Induced Casr Membrane Translomentioning

confidence: 99%

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Integrin-Linked Kinase Is Indispensable for Keratinocyte Differentiation and Epidermal Barrier Function

Sayedyahossein

Rudkouskaya

Leclerc

et al. 2016

Journal of Investigative Dermatology

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A functional permeability barrier is essential to prevent the passage of water and electrolytes, macromolecules, and pathogens through the epidermis. This is accomplished in terminally differentiated keratinocytes through formation of a cornified envelope and the assembly of tight intercellular junctions. Integrin-linked kinase (ILK) is a scaffold protein essential for hair follicle morphogenesis and epidermal attachment to the basement membrane. However, the biological functions of ILK in differentiated keratinocytes remain poorly understood. Furthermore, whether ILK is implicated in keratinocyte differentiation and intercellular junction formation has remained an unresolved issue. Here we describe a pivotal role for ILK in keratinocyte differentiation responses to increased extracellular Ca(2+), regulation of adherens and tight junction assembly, and the formation of an outside-in permeability barrier toward macromolecules. In the absence of ILK, the calcium sensing receptor, E-cadherin, and ZO-1 fail to translocate to the cell membrane, through mechanisms that involve abnormalities in microtubules and in RhoA activation. In situ, ILK-deficient epidermis exhibits reduced tight junction formation and increased outside-in permeability to a dextran tracer, indicating reduced barrier properties toward macromolecules. Therefore, ILK is an essential component of keratinocyte differentiation programs that contribute to epidermal integrity and the establishment of its barrier properties.

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Section: Role Of Microtubules In Ca 2d -Induced Casr Membrane Translomentioning

confidence: 99%

Section: Role Of Microtubules In Ca 2d -Induced Casr Membrane Translomentioning

confidence: 99%

Integrin-Linked Kinase Is Indispensable for Keratinocyte Differentiation and Epidermal Barrier Function

Sayedyahossein

Rudkouskaya

Leclerc

et al. 2016

Journal of Investigative Dermatology

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“…RhoG, a Rho protein related to Rac, has been associated with cell migration, neurite outgrowth, microtubule dynamics, micropinocytosis, bacterial uptake, phagocytosis and leukocyte trans-endothelial migration (deBakker et al, 2004;Ellerbroek et al, 2004;Jackson et al, 2015;Katoh et al, 2006Katoh et al, , 2000van Buul et al, 2007). Recent studies have revealed that RhoG plays a role in tumor cell invasion and may contribute to the formation of invadopodia (Hiramoto-Yamaki et al, 2010;Kwiatkowska et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

A RhoG-mediated signaling pathway that modulates invadopodia dynamics in breast cancer cells

Goicoechea

Zinn

Awadia

et al. 2017

Journal of Cell Science

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One of the hallmarks of cancer is the ability of tumor cells to invade surrounding tissues and metastasize. During metastasis, cancer cells degrade the extracellular matrix, which acts as a physical barrier, by developing specialized actin-rich membrane protrusion structures called invadopodia. The formation of invadopodia is regulated by Rho GTPases, a family of proteins that regulates the actin cytoskeleton. Here, we describe a novel role for RhoG in the regulation of invadopodia disassembly in human breast cancer cells. Our results show that RhoG and Rac1 have independent and opposite roles in the regulation of invadopodia dynamics. We also show that SGEF (also known as ARHGEF26) is the exchange factor responsible for the activation of RhoG during invadopodia disassembly. When the expression of either RhoG or SGEF is silenced, invadopodia are more stable and have a longer lifetime than in control cells. Our findings also demonstrate that RhoG and SGEF modulate the phosphorylation of paxillin, which plays a key role during invadopodia disassembly. In summary, we have identified a novel signaling pathway involving SGEF, RhoG and paxillin phosphorylation, which functions in the regulation of invadopodia disassembly in breast cancer cells.

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“…ILK has been recently shown to complex with ELMO2 and since ILK and RhoG do not bind each other, ELMO2 is thought to be an obligatory bridge in a RhoG/ILK complex (Ho et al, 2009). Furthermore an ELMO2/RhoG/ILK complex has recently been shown to regulate microtubule dynamics downstream of Rac1 activation (Jackson et al, 2015). Thus, it seems plausible that an ELMO2/RhoG/ILK complex may be involved in regulating Rac1 activation in phagocytosis.…”

Section: Discussionmentioning

confidence: 99%

Involvement of Tiam1, RhoG and ELMO2/ILK in Rac1-mediated phagocytosis in human trabecular meshwork cells

Peotter

Phillips

Tong

et al. 2016

Experimental Cell Research

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We previously demonstrated that an αvβ5 integrin/FAK- mediated pathway regulated the phagocytic properties of human trabecular meshwork (HTM) cells. Here we demonstrate that this process is mediated by Rac-1 and a previously unreported signaling pathway that utilizes the Tiam1 as well as a novel ILK/RhoG/ELMO2 signaling pathway. Phagocytosis in both a TM-1 cell line and normal HTM cells was mediated by Rac1 and could be significantly decreased by >75% using the Rac1 inhibitor EHop-016. Knockdown of Rac1 in TM-1 cells also inhibited phagocytosis by 40% whereas overexpression of a constitutively active Rac1 or stimulation with PDGF increased phagocytosis by 83% and 32% respectively. Tiam1 was involved in regulating phagocytosis. Knockdown of Tiam1 inhibited phagocytosis by 72% while overexpression of Tiam1 C1199 increased phagocytosis by 75%. Other upstream effectors of Rac1 found to be involved included ELMO2, RhoG, and ILK. Knockdowns of ELMO2, ILK, and RhoG caused a reduction in phagocytosis by 51%, 55% and 46% respectively. In contrast, knockdown of Vav2 and Dock1 or overexpression of Vav2 Y159/172F did not cause a significant change in phagocytosis. These data suggest a novel link between Tiam1 and RhoG/ILK/ELMO2 pathway as upstream effectors of the Rac1-mediated phagocytic process in TM cells.

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An ELMO2-RhoG-ILK network modulates microtubule dynamics

Cited by 23 publications

References 50 publications

Integrin-Linked Kinase Is Indispensable for Keratinocyte Differentiation and Epidermal Barrier Function

Integrin-Linked Kinase Is Indispensable for Keratinocyte Differentiation and Epidermal Barrier Function

A RhoG-mediated signaling pathway that modulates invadopodia dynamics in breast cancer cells

Involvement of Tiam1, RhoG and ELMO2/ILK in Rac1-mediated phagocytosis in human trabecular meshwork cells

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