The N-terminal DH-PH domain of Trio induces cell spreading and migration by regulating lamellipodia dynamics in a Rac1-dependent fashion.

The guanine-nucleotide exchange factor Trio encodes two DH-PH domains that catalyze nucleotide exchange on Rac1, RhoG and RhoA. The N-terminal DH-PH domain is known to activate Rac1 and RhoG, whereas the C-terminal DH-PH domain can activate RhoA. The current study shows that the N-terminal DH-PH dom...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jos van Rijssel, Mark Hoogenboezem, Lynn Wester, Peter L Hordijk, Jaap D Van Buul
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3ae272e44afc4683861c4904208a2605
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3ae272e44afc4683861c4904208a2605
record_format	dspace
spelling	oai:doaj.org-article:3ae272e44afc4683861c4904208a26052021-11-18T07:30:45ZThe N-terminal DH-PH domain of Trio induces cell spreading and migration by regulating lamellipodia dynamics in a Rac1-dependent fashion.1932-620310.1371/journal.pone.0029912https://doaj.org/article/3ae272e44afc4683861c4904208a26052012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22238672/?tool=EBIhttps://doaj.org/toc/1932-6203The guanine-nucleotide exchange factor Trio encodes two DH-PH domains that catalyze nucleotide exchange on Rac1, RhoG and RhoA. The N-terminal DH-PH domain is known to activate Rac1 and RhoG, whereas the C-terminal DH-PH domain can activate RhoA. The current study shows that the N-terminal DH-PH domain, upon expression in HeLa cells, activates Rac1 and RhoG independently from each other. In addition, we show that the flanking SH3 domain binds to the proline-rich region of the C-terminus of Rac1, but not of RhoG. However, this SH3 domain is not required for Rac1 or RhoG GDP-GTP exchange. Rescue experiments in Trio-shRNA-expressing cells showed that the N-terminal DH-PH domain of Trio, but not the C-terminal DH-PH domain, restored fibronectin-mediated cell spreading and migration defects that are observed in Trio-silenced cells. Kymograph analysis revealed that the N-terminal DH-PH domain, independent of its SH3 domain, controls the dynamics of lamellipodia. Using siRNA against Rac1 or RhoG, we found that Trio-D1-induced lamellipodia formation required Rac1 but not RhoG expression. Together, we conclude that the GEF Trio is responsible for lamellipodia formation through its N-terminal DH-PH domain in a Rac1-dependent manner during fibronectin-mediated spreading and migration.Jos van RijsselMark HoogenboezemLynn WesterPeter L HordijkJaap D Van BuulPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e29912 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jos van Rijssel Mark Hoogenboezem Lynn Wester Peter L Hordijk Jaap D Van Buul The N-terminal DH-PH domain of Trio induces cell spreading and migration by regulating lamellipodia dynamics in a Rac1-dependent fashion.
description	The guanine-nucleotide exchange factor Trio encodes two DH-PH domains that catalyze nucleotide exchange on Rac1, RhoG and RhoA. The N-terminal DH-PH domain is known to activate Rac1 and RhoG, whereas the C-terminal DH-PH domain can activate RhoA. The current study shows that the N-terminal DH-PH domain, upon expression in HeLa cells, activates Rac1 and RhoG independently from each other. In addition, we show that the flanking SH3 domain binds to the proline-rich region of the C-terminus of Rac1, but not of RhoG. However, this SH3 domain is not required for Rac1 or RhoG GDP-GTP exchange. Rescue experiments in Trio-shRNA-expressing cells showed that the N-terminal DH-PH domain of Trio, but not the C-terminal DH-PH domain, restored fibronectin-mediated cell spreading and migration defects that are observed in Trio-silenced cells. Kymograph analysis revealed that the N-terminal DH-PH domain, independent of its SH3 domain, controls the dynamics of lamellipodia. Using siRNA against Rac1 or RhoG, we found that Trio-D1-induced lamellipodia formation required Rac1 but not RhoG expression. Together, we conclude that the GEF Trio is responsible for lamellipodia formation through its N-terminal DH-PH domain in a Rac1-dependent manner during fibronectin-mediated spreading and migration.
format	article
author	Jos van Rijssel Mark Hoogenboezem Lynn Wester Peter L Hordijk Jaap D Van Buul
author_facet	Jos van Rijssel Mark Hoogenboezem Lynn Wester Peter L Hordijk Jaap D Van Buul
author_sort	Jos van Rijssel
title	The N-terminal DH-PH domain of Trio induces cell spreading and migration by regulating lamellipodia dynamics in a Rac1-dependent fashion.
title_short	The N-terminal DH-PH domain of Trio induces cell spreading and migration by regulating lamellipodia dynamics in a Rac1-dependent fashion.
title_full	The N-terminal DH-PH domain of Trio induces cell spreading and migration by regulating lamellipodia dynamics in a Rac1-dependent fashion.
title_fullStr	The N-terminal DH-PH domain of Trio induces cell spreading and migration by regulating lamellipodia dynamics in a Rac1-dependent fashion.
title_full_unstemmed	The N-terminal DH-PH domain of Trio induces cell spreading and migration by regulating lamellipodia dynamics in a Rac1-dependent fashion.
title_sort	n-terminal dh-ph domain of trio induces cell spreading and migration by regulating lamellipodia dynamics in a rac1-dependent fashion.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/3ae272e44afc4683861c4904208a2605
work_keys_str_mv	AT josvanrijssel thenterminaldhphdomainoftrioinducescellspreadingandmigrationbyregulatinglamellipodiadynamicsinarac1dependentfashion AT markhoogenboezem thenterminaldhphdomainoftrioinducescellspreadingandmigrationbyregulatinglamellipodiadynamicsinarac1dependentfashion AT lynnwester thenterminaldhphdomainoftrioinducescellspreadingandmigrationbyregulatinglamellipodiadynamicsinarac1dependentfashion AT peterlhordijk thenterminaldhphdomainoftrioinducescellspreadingandmigrationbyregulatinglamellipodiadynamicsinarac1dependentfashion AT jaapdvanbuul thenterminaldhphdomainoftrioinducescellspreadingandmigrationbyregulatinglamellipodiadynamicsinarac1dependentfashion AT josvanrijssel nterminaldhphdomainoftrioinducescellspreadingandmigrationbyregulatinglamellipodiadynamicsinarac1dependentfashion AT markhoogenboezem nterminaldhphdomainoftrioinducescellspreadingandmigrationbyregulatinglamellipodiadynamicsinarac1dependentfashion AT lynnwester nterminaldhphdomainoftrioinducescellspreadingandmigrationbyregulatinglamellipodiadynamicsinarac1dependentfashion AT peterlhordijk nterminaldhphdomainoftrioinducescellspreadingandmigrationbyregulatinglamellipodiadynamicsinarac1dependentfashion AT jaapdvanbuul nterminaldhphdomainoftrioinducescellspreadingandmigrationbyregulatinglamellipodiadynamicsinarac1dependentfashion
_version_	1718423340001001472

The N-terminal DH-PH domain of Trio induces cell spreading and migration by regulating lamellipodia dynamics in a Rac1-dependent fashion.

Ejemplares similares