Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Biol Chem ; 288(4): 2179-89, 2013 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-23235160

RESUMO

Cell-cell adhesions and the cytoskeletons play important and coordinated roles in cell biology, including cell differentiation, development, and migration. Adhesion and cytoskeletal dynamics are regulated by Rho-GTPases. ARHGAP21 is a negative regulator of Rho-GTPases, particularly Cdc42. Here we assess the function of ARHGAP21 in cell-cell adhesion, cell migration, and scattering. We find that ARHGAP21 is localized in the nucleus, cytoplasm, or perinuclear region but is transiently redistributed to cell-cell junctions 4 h after initiation of cell-cell adhesion. ARHGAP21 interacts with Cdc42, and decreased Cdc42 activity coincides with the appearance of ARHGAP21 at the cell-cell junctions. Cells lacking ARHGAP21 expression show weaker cell-cell adhesions, increased cell migration, and a diminished ability to undergo hepatocyte growth factor-induced epithelial-mesenchymal transition (EMT). In addition, ARHGAP21 interacts with α-tubulin, and it is essential for α-tubulin acetylation in EMT. Our findings indicate that ARHGAP21 is a Rho-GAP involved in cell-cell junction remodeling and that ARHGAP21 affects migration and EMT through α-tubulin interaction and acetylation.


Assuntos
Transição Epitelial-Mesenquimal , Epitélio/metabolismo , Proteínas Ativadoras de GTPase/fisiologia , Tubulina (Proteína)/metabolismo , Acetilação , Animais , Adesão Celular , Comunicação Celular , Linhagem Celular Tumoral , Movimento Celular , Cães , Proteínas Ativadoras de GTPase/metabolismo , Humanos , Células Madin Darby de Rim Canino , Metástase Neoplásica , Interferência de RNA , Fatores de Tempo , Proteína cdc42 de Ligação ao GTP/metabolismo
2.
J Cell Sci ; 125(Pt 17): 4001-13, 2012 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22685327

RESUMO

Hepatocyte growth factor (HGF) signaling drives epithelial cells to scatter by breaking cell-cell adhesions and causing them to migrate as solitary cells, a process that parallels epithelial-mesenchymal transition. HGF binds and activates the c-met receptor tyrosine kinase, but downstream signaling required for scattering remains poorly defined. We have applied a chemical biology approach to identify components of HGF signaling that are required for scattering in an in vitro model system. This approach yields a number of small molecules that block HGF-induced scattering, including a calcium channel blocker. We show that HGF stimulation results in sudden and transient increases in ion channel influxes at the plasma membrane. Although multiple channels occur in the membranes of our model system, we find that TrpC6 is specifically required for HGF-induced scattering. We further demonstrate that HGF-induced ion influxes through TrpC6 channels coincide with a transient increase in nuclear factor of activated T-cells (NFAT)-dependent gene transcription and that NFAT-dependent gene transcription is required for HGF-induced cell scattering.


Assuntos
Membrana Celular/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Íons/metabolismo , Fatores de Transcrição NFATC/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Transcrição Gênica , Actinas/metabolismo , Animais , Cálcio/metabolismo , Membrana Celular/efeitos dos fármacos , Cães , Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fator de Crescimento de Hepatócito/farmacologia , Células Madin Darby de Rim Canino , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Reprodutibilidade dos Testes , Transdução de Sinais/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Canais de Cátion TRPC/metabolismo , Canais de Cátion TRPV/metabolismo , Transcrição Gênica/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...