Direct Binding of the Na–H Exchanger NHE1 to ERM Proteins Regulates the Cortical Cytoskeleton and Cell Shape Independently of H+ Translocation

Denker, Sheryl P.; Huang, Derek C; Orlowski, John; Furthmayr, Heinz; Barber, Diane L.

doi:10.1016/s1097-2765(00)00139-8

Cited by 382 publications

(482 citation statements)

References 57 publications

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“…In contrast, in migrating fibroblasts, NHE1 concentrates at the leading edge of the cell along the border of lamellipodia [41,40]. NHE1 abundance at the plasma membrane was recently shown to be regulated by direct ubiquitylation of the exchanger [154].…”

Section: Slc9a1-nhe1mentioning

confidence: 99%

“…NHE1 also participates in cell migration [82,40,41,150,79]. Inhibition or genetic ablation of NHE1 from fibroblasts significantly reduces migration speed and inhibits chemotaxis.…”

Section: Slc9a1-nhe1mentioning

confidence: 99%

“…Inhibition or genetic ablation of NHE1 from fibroblasts significantly reduces migration speed and inhibits chemotaxis. Both ion translocation and anchoring of cytoskeletal proteins through the intracellular NHE1 C-terminus are required [41].…”

Section: Slc9a1-nhe1mentioning

confidence: 99%

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Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Fuster

Alexander

2013

Pflugers Arch - Eur J Physiol

137

122

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The SLC9 gene family encodes Na + /H + exchangers (NHEs). These transmembrane proteins transport ions across lipid bilayers in a diverse array of species from prokaryotes to eukaryotes, including plants, fungi and animals. They utilize the electrochemical gradient of one ion to transport another ion against its electrochemical gradient. Currently, 13 evolutionarily conserved NHE isoforms are known in mammals [46,22,128]. The SLC9 gene family (solute carrier classification of transporters:www.bioparadigms.org) is divided into three subgroups [46]. The SLC9A subgroup encompasses plasmalemmal isoforms NHE1-5 (SLC9A1-5) and the predominantly intracellular isoforms NHE6-9 (SLC9A6-9). The SLC9B subgroup consists of two recently cloned isoforms, NHA1 and NHA2 (SLC9B1 and SLC9B2, respectively). The SLC9C subgroup consist of a sperm specific plasmalemmal NHE (SLC9C1) and a putative NHE, SLC9C2, for which there is currently no functional data [46].NHEs participate in the regulation of cytosolic and organellar pH as well as cell volume. In the intestine and kidney, NHEs are critical for transepithelial movement of Na + and HCO 3 -and thus for whole body volume and acid-base homeostasis [46]. Mutations in the NHE6 or NHE9 genes cause neurological disease in humans and are currently the only NHEs directly linked to human disease.However, it is becoming increasingly apparent that members of this gene family contribute to the pathophysiology of multiple human diseases.

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Section: Slc9a1-nhe1mentioning

confidence: 99%

“…NHE1 also participates in cell migration [82,40,41,150,79]. Inhibition or genetic ablation of NHE1 from fibroblasts significantly reduces migration speed and inhibits chemotaxis.…”

Section: Slc9a1-nhe1mentioning

confidence: 99%

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Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Fuster

Alexander

2013

Pflugers Arch - Eur J Physiol

137

122

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“…Ezrin, for example, can associate with various membrane proteins such as CD44 (Tsukita et al, 1994), intercellular adhesion molecule-1,2 (Helander et al, 1996), Na-H exchanger (Denker et al, 2000), and type II c-AMP-dependent protein kinases (Dransfield et al, 1997). These interactions are established via its N terminus, whereas its C-terminal domain binds to F-actin in vitro (Turunen et al, 1994) and in vivo (Algrain et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Hepatocyte Growth Factor-induced Ras Activation Requires ERM Proteins Linked to Both CD44v6 and F-Actin

Orian-Rousseau

Morrison

Matzke

et al. 2007

MBoC

178

181

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In several types of cells, the activation of the receptor tyrosine kinase c-Met by its ligand hepatocyte growth factor (HGF) requires the coreceptor CD44v6. The CD44 extracellular domain is necessary for c-Met autophosphorylation, whereas the intracellular domain is required for signal transduction. We have already shown that the CD44 cytoplasmic tail recruits ezrin, radixin and moesin (ERM) proteins to the complex of CD44v6, c-Met, and HGF. We have now defined the function of the ERM proteins and the step they promote in the signaling cascade. The association of ERM proteins to the coreceptor is absolutely required to mediate the HGF-dependent activation of Ras by the guanine nucleotide exchange factor Sos. The ERM proteins need, in addition, to be linked to the actin cytoskeleton to catalyze the activation of Ras. Thus, we describe here a new function of the cytoskeleton. It is part of a "signalosome" complex that organizes the activation of Ras by Sos. So far the cytoskeleton has mainly been identified as a "responder" to signal transduction. Here, we show now that F-actin acts as an "inducer" that actively organizes the signaling cascade.

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“…and osmotic cell shrinkage [31] . NHE1 deficiency leads to growth retardation, ataxia, and seizures [2] as well as abnormal cell morphology and adhesion [32] . It is reported that the asymmetrical expression and activation of NHE1 in cells generates a local intracellular pH gradient and thus induces or at least supports the rearrangement of the cytoskeleton by affecting cofilin, an actin-binding protein that increases the recycling of actin monomers [1] .…”

Section: Vacuolar Type H + -Atpases (V-atpases) Vacuolarmentioning

confidence: 99%

Proton production, regulation and pathophysiological roles in the mammalian brain

Zeng

2012

Neurosci. Bull.

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Abstract:The recent demonstration of proton signaling in C. elegans muscle contraction suggests a novel mechanism for proton-based intercellular communication and has stimulated enthusiasm for exploring proton signaling in higher organisms. Emerging evidence indicates that protons are produced and regulated in localized space and time. Furthermore, identification of proton regulators and sensors in the brain leads to the speculation that proton production and regulation may be of major importance for both physiological and pathological functions ranging from nociception to learning and memory. Extracellular protons may play a role in signal transmission by not only acting on adjacent cells but also affecting the cell from which they were released. In this review, we summarize the upstream and downstream pathways of proton production and regulation in the mammalian brain, with special emphasis on the proton extruders and sensors that are critical in the homeostatic regulation of pH, and discuss their potential roles in proton signaling under normal and pathophysiological conditions.

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Direct Binding of the Na–H Exchanger NHE1 to ERM Proteins Regulates the Cortical Cytoskeleton and Cell Shape Independently of H+ Translocation

Cited by 382 publications

References 57 publications

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Hepatocyte Growth Factor-induced Ras Activation Requires ERM Proteins Linked to Both CD44v6 and F-Actin

Proton production, regulation and pathophysiological roles in the mammalian brain

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