IQGAP1 Regulates Endothelial Barrier Function via EB1-Cortactin Cross Talk

Tian, Yufeng; Tian, Xinxin; Gawlak, Grzegorz; O’Donnell, James J.; Sacks, David B.; Birukova, Anna A.

doi:10.1128/mcb.00248-14

Cited by 34 publications

(42 citation statements)

References 37 publications

(50 reference statements)

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“…HGF stimulation strengthens barrier function in some cell types, e.g., endothelial cells [57]. siRNA knockdown of IQGAP1 or Rac1 attenuates HGF-induced increase in endothelial barrier strength [58]. HGF induced the formation of a Rac-1 dependent complex containing IQGAP1, EB1 and cortactin.…”

Section: Iqgap1 Modulates Cellular Signalingmentioning

confidence: 99%

“…HGF induced the formation of a Rac-1 dependent complex containing IQGAP1, EB1 and cortactin. Cortactin promotes actin polymerization, and the complex is necessary for cortical actin remodeling and peripheral microtubule growth that are required for strengthening barrier functions [58]. These findings indicate that IQGAP1 functions as a scaffold between actin and microtubules to promote enhanced barrier functions downstream of HGF.…”

Section: Iqgap1 Modulates Cellular Signalingmentioning

confidence: 99%

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IQGAPs choreograph cellular signaling from the membrane to the nucleus

Smith

Hedman

Sacks

2015

Trends in Cell Biology

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138

154

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Since its discovery in 1994, cellular functions for the scaffold protein IQGAP1 have expanded immensely. Over 100 unique IQGAP1 interacting proteins have been identified, implicating IQGAP1 as a critical integrator of cellular signaling pathways. Initial research established functions for IQGAP1 in cell-cell adhesion, cell migration, and cell signaling. Recent studies have revealed additional IQGAP1 binding partners, expanding the biological roles of IQGAP1. These include crosstalk between signaling cascades, regulation of nuclear function, and Wnt pathway potentiation. Investigation of the IQGAP2 and IQGAP3 homologues demonstrate unique functions, some of which differ from those of IQGAP1. Summarized here are recent observations that enhance our understanding of IQGAP proteins in integrating diverse signaling pathways.

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Section: Iqgap1 Modulates Cellular Signalingmentioning

confidence: 99%

Section: Iqgap1 Modulates Cellular Signalingmentioning

confidence: 99%

IQGAPs choreograph cellular signaling from the membrane to the nucleus

Smith

Hedman

Sacks

2015

Trends in Cell Biology

Self Cite

138

154

View full text Add to dashboard Cite

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“…Our published studies also show HGF-induced interactions between cortactin, EB1, and multifunctional scaffold protein IQGAP1 [17]. Next experiments tested the role of EB1 in the HGF-induced peripheral accumulation of IQGAP1-dependent activators of actin polymerization, WAVE and p21Arc [29, 30], and assembly of WAVE-p21Arc-IQGAP1 complex.…”

Section: Resultsmentioning

confidence: 88%

“…We recently found that HGF stimulation caused pronounced peripheral MT growth in pulmonary EC. Growing MT tips reached the cell cortex, where they became captured by multifunctional scaffold IQGAP1 [17]. These findings suggest that EB1 is required for peripheral targeting of signaling molecules, which leads to activation of cytoskeletal and cell junction remodeling.…”

Section: Discussionmentioning

confidence: 99%

“…Using HGF as a model agonist, which enhances basal EC barrier properties by activating Rac1 pathway [15, 16], we found that HGF promoted peripheral MT growth and MT protrusion to the EC peripheral compartment [17]. HGF-induced MT growth led to translocation of the MT-associated Rac1-specific GEF Asef to the cell periphery and local stimulation of Rac1 signaling [18].…”

Section: Introductionmentioning

confidence: 99%

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Role of End Binding Protein-1 in endothelial permeability response to barrier-disruptive and barrier-enhancing agonists

Tian

Ohmura

Shah

et al. 2017

Cellular Signalling

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Rapid changes in microtubule (MT) polymerization dynamics affect regional activity of small GTPases RhoA and Rac1, which play a key role in the regulation of actin cytoskeleton and endothelial cell (EC) permeability. This study tested the role of End Binding protein-1 (EB1) in the mechanisms of increased and decreased EC permeability caused by thrombin and hepatocyte growth factor (HGF) and mediated by RhoA and Rac1 GTPases, respectively. Stimulation of human lung EC with thrombin inhibited peripheral MT growth, which was monitored by morphological and biochemical evaluation of peripheral MT and the levels of stabilized MT. In contrast, stimulation of EC with HGF promoted peripheral MT growth and protrusion of EB1-positive MT plus ends to the EC peripheral submembrane area. EB1 knockdown by small interfering RNA did not affect partial MT depolymerization, activation of Rho signaling, and permeability response to thrombin, but suppressed the HGF-induced endothelial barrier enhancement. EB1 knockdown suppressed HGF-induced activation of Rac1 and Rac1 cytoskeletal effectors cortactin and PAK1, impaired HGF-induced assembly of cortical cytoskeleton regulatory complex (WAVE-p21Arc-IQGAP1), and blocked HGF-induced enhancement of peripheral actin cytoskeleton and VE-cadherin-positive adherens junctions. Altogether, these data demonstrate a role for EB1 in coordination of MT-dependent barrier enhancement response to HGF, but show no involvement of EB1 in acute increase of EC permeability caused by the barrier disruptive agonist. The results suggest that increased peripheral EB1 distribution is a critical component of the Rac1-mediated pathway and peripheral cytoskeletal remodeling essential for agonist-induced EC barrier enhancement.

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Molecular Regulation of Sprouting Angiogenesis

Duran

Howell

Dave

et al. 2017

Comprehensive Physiology

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The term angiogenesis arose in the 18th century. Several studies over the next 100 years laid the groundwork for initial studies performed by the Folkman laboratory, which were at first met with some opposition. Once overcome, the angiogenesis field has flourished due to studies on tumor angiogenesis and various developmental models that can be genetically manipulated, including mice and zebrafish. In addition, new discoveries have been aided by the ability to isolate primary endothelial cells, which has allowed dissection of various steps within angiogenesis. This review will summarize the molecular events that control angiogenesis downstream of biochemical factors such as growth factors, cytokines, chemokines, hypoxia-inducible factors (HIFs), and lipids. These and other stimuli have been linked to regulation of junctional molecules and cell surface receptors. In addition, the contribution of cytoskeletal elements and regulatory proteins has revealed an intricate role for mobilization of actin, microtubules, and intermediate filaments in response to cues that activate the endothelium. Activating stimuli also affect various focal adhesion proteins, scaffold proteins, intracellular kinases, and second messengers. Finally, metalloproteinases, which facilitate matrix degradation and the formation of new blood vessels, are discussed, along with our knowledge of crosstalk between the various subclasses of these molecules throughout the text. Compr Physiol 8:153-235, 2018.

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IQGAP1 Regulates Endothelial Barrier Function via EB1-Cortactin Cross Talk

Cited by 34 publications

References 37 publications

IQGAPs choreograph cellular signaling from the membrane to the nucleus

IQGAPs choreograph cellular signaling from the membrane to the nucleus

Role of End Binding Protein-1 in endothelial permeability response to barrier-disruptive and barrier-enhancing agonists

Molecular Regulation of Sprouting Angiogenesis

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