High impact information on Hgs

• Moreover, recombinant Hrs-2 inhibits calcium-triggered 3H-noradrenaline release from permeabilized PC12 cells [1].
• Furthermore, Hrs-2 binds and hydrolyses nucleoside triphosphates with kinetics that suggest that ATP is the physiological substrate for this enzyme [1].
• The binding of Hrs-2 to SNAP-25 is inhibited by calcium in the physiological concentration range that supports synaptic transmission [1].
• Hrs-2, via interactions with SNAP-25, plays a regulatory role on the exocytic machinery [2].
• We now show that Hrs-2 physically interacts with Eps15, a protein required for receptor-mediated endocytosis [2].

Biological context of Hgs

• Moreover, overexpression of Hrs in PC12 cells inhibits Ca(2+)-dependent exocytosis [3].
• The deduced amino acid sequences revealed a strikingly high homology to a mouse hepatocyte growth factor-regulated tyrosine kinase substrate but no homology to CGT [4].
• To examine whether Hrs-2 is expressed in rat kidney, we carried out RT-PCR combined with DNA sequence analysis and Northern blotting using a digoxigenin-labeled Hrs-2 RNA probe [5].

Anatomical context of Hgs

• Studies using indirect immunofluorescence and confocal microscopy reveal that, in addition to early endosomes, Hrs is also localized to large dense-core secretory granules and synaptic-like microvesicles in nerve growth factor-differentiated PC12 cells [3].
• Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) is required for trafficking of cell surface receptors to the lysosome [6].
• Immunoelectron microscopy reveals Hrs-2 localization on the limiting membrane of multivesicular bodies, organelles in the endosomal pathway [2].
• Colabeling with AQP2 revealed colocalization in vesicles and apical plasma membrane domains, suggesting a role for Hrs-2 in regulated AQP2 trafficking [5].
• SNAP-25-associated Hrs-2 protein colocalizes with AQP2 in rat kidney collecting duct principal cells [5].

Associations of Hgs with chemical compounds

• Hrs-2 immunoreactivity was observed in collecting duct principal cells, and weaker labeling was detected in other nephron segments [5].
• Estrogen treatment (0.25 mg estradiol) significantly decreased SNAP-25a (32%; 10%) and SNAP-25b (25%; 22%) mRNA levels in the anterior and intermediate lobes, respectively, whereas VAMP-2, munc-18 and Hrs-2 mRNA levels remained unchanged [7].
• Endocytosed TrkB-FL receptors recycle to a lesser extent in a hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-dependent manner which relies on its tyrosine kinase activity [8].

Other interactions of Hgs

• Large varicosities containing VAMP-2- and Hrs-2 immunocreactivity were seen in salt-loaded animals [9].
• The presence of Hrs-2 protein in rat kidney was confirmed by immunoblotting, revealing a 115-kDa protein in kidney and brain membrane fractions corresponding to the expected molecular size of Hrs-2 [5].
• Immunostaining and confocal laser scanning microscopy of LLC-PK(1) cells (a porcine proximal tubule cell line) transfected with Hrs-2 DNA confirmed the specificity of the antibody and revealed that Hrs-2 is mainly localized in intracellular compartments, including cathepsin D-containing lysosomal/endosomal compartments [5].

Analytical, diagnostic and therapeutic context of Hgs

• RT-PCR and Northern blotting revealed that Hrs-2 mRNA is localized in all zones of rat kidney [5].
• The cellular and subcellular localization of Hrs-2 in rat kidney was examined by immunocytochemistry and confocal laser scanning microscopy [5].

References