Intramolecular Interactions between the Dbl Homology (DH) Domain and the Carboxyl-terminal region of Myosin II-interacting Guanine Nucleotide Exchange Factor (MyoGEF) Act as an Autoinhibitory Mechanism for the Regulation of MyoGEF Functions

Wu, Di; Jiao, Meng; Zu, Shicheng; Sollecito, Christopher C.; Jimenez-Cowell, Kevin; Mold, Alexander J.; Kennedy, Ryan M.; Wei, Qize

doi:10.1074/jbc.m114.607267

Cited by 2 publications

(3 citation statements)

References 76 publications

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“…However, exogenous expression of GFP-MYOGEF-FL or GFP-MYOGEF-1–752 did not alter membrane blebbing in transfected M2 melanoma cells ( Figure 3D , compare panels a and g with panel d; Figure 3F ). We have shown previously that the C-terminal region of MYOGEF interacts with its N-terminal region, forming an inhibitory conformation ( Wu et al. , 2014b ).…”

Section: Resultsmentioning

confidence: 99%

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Myosin II–interacting guanine nucleotide exchange factor promotes bleb retraction via stimulating cortex reassembly at the bleb membrane

Jiao

Wei

2018

MBoC

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Blebs are involved in various biological processes such as cell migration, cytokinesis, and apoptosis. While the expansion of blebs is largely an intracellular pressure-driven process, the retraction of blebs is believed to be driven by RhoA activation that leads to the reassembly of the actomyosin cortex at the bleb membrane. However, it is still poorly understood how RhoA is activated at the bleb membrane. Here, we provide evidence demonstrating that myosin II–interacting guanine nucleotide exchange factor (MYOGEF) is implicated in bleb retraction via stimulating RhoA activation and the reassembly of an actomyosin network at the bleb membrane during bleb retraction. Interaction of MYOGEF with ezrin, a well-known regulator of bleb retraction, is required for MYOGEF localization to retracting blebs. Notably, knockout of MYOGEF or ezrin not only disrupts RhoA activation at the bleb membrane, but also interferes with nonmuscle myosin II localization and activation, as well as actin polymerization in retracting blebs. Importantly, MYOGEF knockout slows down bleb retraction. We propose that ezrin interacts with MYOGEF and recruits it to retracting blebs, where MYOGEF activates RhoA and promotes the reassembly of the cortical actomyosin network at the bleb membrane, thus contributing to the regulation of bleb retraction.

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Section: Resultsmentioning

confidence: 99%

“…GFP-MYOGEF and GFP-NMHC-IIA were generated as described previously ( Wei and Adelstein, 2000 ; Wu et al. , 2006 , 2014b ). GFP-N1-ezrin was used as a PCR template to amplify the N-terminal region of ezrin (residues 1–320), which, in turn, was cloned into pDEST17 (Thermo Fisher Scientific) to generate His-ezrin-1–320.…”

Section: Methodsmentioning

confidence: 99%

Myosin II–interacting guanine nucleotide exchange factor promotes bleb retraction via stimulating cortex reassembly at the bleb membrane

Jiao

Wei

2018

MBoC

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“…To assess the effect of DEPDC1B on actin polymerization induced by TRIOGEFD1 (the RAC1-specific GEF domain of TRIO), the transfected HeLa cells were stained with Alexa Fluor 594 phalloidin and the fluorescence intensities in transfected cells were quantitated using the NIH ImageJ software [30, 31]. Briefly, the freehand selection tool was used to mark the cells of interest in the same field.…”

Section: Methodsmentioning

confidence: 99%

Identification of the GTPase-activating protein DEP domain containing 1B (DEPDC1B) as a transcriptional target of Pitx2

Zhu

Jimenez-Cowell

et al. 2015

Experimental Cell Research

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Pitx2 is a bicoid-related homeobox transcription factor implicated in regulating left-right patterning and organogenesis. However, only a limited number of Pitx2 downstream target genes have been identified and characterized. Here we demonstrate that Pitx2 is a transcriptional repressor of DEP domain containing 1B (DEPDC1B). The first intron of the human and mouse DEP domain containing 1B genes contains multiple consensus DNA-binding sites for Pitx2. Chromatin immunoprecipitation assays revealed that Pitx2, along with histone deacetylase 1, was recruited to the first intron of Depdc1b. In contrast, RNAi-mediated depletion of Pitx2 not only enhanced the acetylation of histone H4 in the first intron of Depdc1b, but also increased the protein level of Depdc1b. Luciferase reporter assays also showed that Pitx2 could repress the transcriptional activity mediated by the first intron of human DEPDC1B. The GAP domain of DEPDC1B interacted with nucleotide-bound forms of RAC1 in vitro. In addition, exogenous expression of DEPDC1B suppressed RAC1 activation and interfered with actin polymerization induced by the guanine nucleotide exchange factor TRIO. Moreover, DEPDC1B interacted with various signaling molecules such as U2af2, Erh, and Salm. We propose that Pitx2-mediated repression of Depdc1b expression contributes to the regulation of multiple molecular pathways, such as Rho GTPase signaling.

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Intramolecular Interactions between the Dbl Homology (DH) Domain and the Carboxyl-terminal region of Myosin II-interacting Guanine Nucleotide Exchange Factor (MyoGEF) Act as an Autoinhibitory Mechanism for the Regulation of MyoGEF Functions

Cited by 2 publications

References 76 publications

Myosin II–interacting guanine nucleotide exchange factor promotes bleb retraction via stimulating cortex reassembly at the bleb membrane

Myosin II–interacting guanine nucleotide exchange factor promotes bleb retraction via stimulating cortex reassembly at the bleb membrane

Identification of the GTPase-activating protein DEP domain containing 1B (DEPDC1B) as a transcriptional target of Pitx2

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