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Hideki Yamaguchi

Publications and source records attributed to Hideki Yamaguchi.

21 records · Page 2Linked to original sources

A role for neuropeptide W in the regulation of feeding behavior.

Neuropeptide W (NPW) is a novel hypothalamic peptide that activates the previously described orphan G protein-coupled receptors, GPR7 and GPR8. Two endogenous molecular forms of NPW that consist of 23- and 30-amino acid residues were identified. The localization of GPR7 and GPR8 in some hypothalamic regions of primary importance in the regulation of feeding behavior has provided a springboard for investigation of the role of NPW in the central nervous system. In this study we examined the effects of NPW on feeding and energy expenditure in rats. Single intracerebroventricular (i.c.v.) administration of NPW23 and NPW30 to free-feeding rats suppressed dark phase and fasting-induced food intake at similar effective doses. Continuous i.c.v. infusion of NPW using an osmotic minipump suppressed feeding and body weight gain over the infusion period. Conversely, i.c.v. administration of anti-NPW IgG stimulated feeding. Furthermore, i.c.v. administration of NPW increased body temperature and heat production. These data raise the possibility that NPW functions as an endogenous catabolic signaling molecule in the brain. Further investigation of the biochemical and physiological functions of NPW will help us to better understand the hypothalamic regulation of energy homeostasis.

Animals↗

Two verprolin homology domains increase the Arp2/3 complex-mediated actin polymerization activities of N-WASP and WAVE1 C-terminal regions.

WASP family proteins induce actin polymerization through a C-terminal verprolin homology, cofilin homology, and acidic (VCA) region by activating the Arp2/3 complex. The N-WASP VCA region is the most potent activator of the Arp2/3 complex. In addition, full-length WAVE1 and a WAVE1 VCA fragment show differential activity. The mechanisms underlying these differences are poorly understood. We examined the activities of various N-WASP and WAVE1 VCA mutant proteins with several types of fusion moieties. When fused to GST, maltose-binding protein, or the WAVE1 proline-rich domain, N-WASP VCA and WAVE1 VCA mutant proteins with two V motifs showed stronger activities than wild-type WAVE1 VCA with one V motif, demonstrating the importance of two V motifs for strong VCA activity. A WAVE1 VCA fragment tagged with six histidines (His) showed markedly reduced activity compared to GST-fused VCA, whereas His-tagged N-WASP VCA showed similar activity to GST-fused VCA. An additional V motif failed to enhance WAVE1 VCA activity in the His-tagged form. Thus, the WAVE1 VCA fragment may exist in an unfavorable conformation to activate the Arp2/3 complex, implying the existence of a structural difference between WAVE1 and N-WASP VCAs in addition to the number of V motifs.

Actin-Related Protein 2↗

Neural Wiskott-Aldrich syndrome protein is involved in hepatocyte growth factor-induced migration, invasion, and tubulogenesis of epithelial cells.

Neural Wiskott-Aldrich syndrome protein (N-WASP), a member of the WASP family, regulates reorganization of the actin cytoskeleton through activation of the Arp2/3 complex. To date, most studies of N-WASP have focused on intracellular and morphological phenomena, such as vesicle transport and filopodium formation. We investigated the importance of N-WASP in epithelial morphogenesis, using Madin-Darby canine kidney epithelial cells, which form branching tubules when cultured with hepatocyte growth factor (HGF) in collagen gel. We established MDCK cell lines that overexpress wild-type N-WASP (WT-NW) or a dominant-negative form of N-WASP (DN-NW). WT-NW and parental Madin-Darby canine kidney cells formed branching tubules in collagen gel in response to HGF. However, formation of branching tubules was suppressed in DN-NW cells. During tubulogenesis, endogenous N-WASP accumulated at cell extensions protruding from the walls of the cysts and at the tips of the extending tubules. Gross cell morphology, cell-cell adhesion, cell polarity, and scattering in response to HGF were unaffected in WT-NW and DN-NW cells. In contrast, directed cell migration and HGF-induced invasion were significantly repressed in DN-NW cells. These results indicate that N-WASP regulates HGF-induced cell migration and invasion, which are required for epithelial tubulogenesis.

Animals↗