Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.25 (triphosphatase)
 1,529 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A fundamental feature of cell polarity in response to spatial cues is asymmetric amplification of molecules generated by positive feedback signaling. We report a positive feedback loop between the guanosine triphosphatase Cdc42, a central determinant in eukaryotic cell polarity, and H(+) efflux by Na-H(+) exchanger 1 (NHE1), which is necessary at the front of migrating cells for polarity and directional motility. In response to migratory cues, Cdc42 is not activated in fibroblasts expressing a mutant NHE1 that lacks H(+) efflux, and wild-type NHE1 is not activated in fibroblasts expressing mutationally inactive Cdc42-N17. H(+) efflux by NHE1 is not necessary for release of Cdc42-guanosine diphosphate (GDP) from Rho GDP dissociation inhibitor or for the membrane recruitment of Cdc42 but is required for GTP binding by Cdc42 catalyzed by a guanine nucleotide exchange factor (GEF). Data indicate that GEF binding to phosphotidylinositol 4,5-bisphosphate is pH dependent, suggesting a mechanism for how H(+) efflux by NHE1 promotes Cdc42 activity to generate a positive feedback signal necessary for polarity in migrating cells.
 ...
PMID:Positive feedback between Cdc42 activity and H+ efflux by the Na-H exchanger NHE1 for polarity of migrating cells. 1798 18

Sarcolemmal Na(+) /H(+) exchanger 1 (NHE1) activity is essential for the intracellular pH (pHi ) homeostasis in cardiac myocytes. Emerging evidence indicates that sarcolemmal NHE1 dysfunction was closely related to cardiomyocyte death, but it remains unclear whether defective trafficking of NHE1 plays a role in the vital cellular signalling processes. Dynamin (DNM), a large guanosine triphosphatase (GTPase), is best known for its roles in membrane trafficking events. Herein, using co-immunoprecipitation, cell surface biotinylation and confocal microscopy techniques, we investigated the potential regulation on cardiac NHE1 activity by DNM. We identified that DNM2, a cardiac isoform of DNM, directly binds to NHE1. Overexpression of a wild-type DNM2 or a dominant-negative DNM2 mutant with defective GTPase activity in adult rat ventricular myocytes (ARVMs) facilitated or retarded the internalization of sarcolemmal NHE1, whereby reducing or increasing its activity respectively. Importantly, the increased NHE1 activity associated with DNM2 deficiency led to ARVMs apoptosis, as demonstrated by cell viability, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay, Bcl-1/Bax expression and caspase-3 activity, which were effectively rescued by pharmacological inhibition of NHE1 with zoniporide. Thus, our results demonstrate that disruption of the DNM2-dependent retrograde trafficking of NHE1 contributes to cardiomyocyte apoptosis.
...
PMID:Aberrant dynamin 2-dependent Na(+) /H(+) exchanger-1 trafficking contributes to cardiomyocyte apoptosis. 2383 75