RhoB regulates cell migration through altered focal adhesion dynamics.
The Rho GTPase RhoB has been shown to affect cell migration, but how it does this is not clear. Here we show that cells depleted of RhoB by RNAi are rounded and have defects in Rac-mediated spreading and lamellipodium extension, although they have active membrane ruffling around the periphery. Depletion of the exchange factor GEF-H1 induces a similar phenotype. RhoB-depleted cells migrate faster, but less persistently in a chemotactic gradient, and frequently round up during migration. RhoB-depleted cells have similar numbers of focal adhesions to control cells during spreading and migration, but show more diffuse and patchy contact with the substratum. They have lower levels of surface β1 integrin, and β1 integrin activity is reduced in actin-rich protrusions. We propose that RhoB contributes to directional cell migration by regulating β1 integrin surface levels and activity, thereby stabilizing lamellipodial protrusions.
Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
Francisco M
FM
Vega
Audrey
A
Colomba
Nicolas
N
Reymond
Mairian
M
Thomas
Anne J
AJ
Ridley
D000230:Adenocarcinoma / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D048430:Cell Shape; D005260:Female; D022001:Focal Adhesions / Q000502:physiology*; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology; D006160:Guanosine Triphosphate / Q000502:physiology; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D008297:Male; D008870:Microtubules / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000473:pathology; D011554:Pseudopodia / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D064067:Rho Guanine Nucleotide Exchange Factors; D020830:rac1 GTP-Binding Protein / Q000502:physiology; D020743:rhoB GTP-Binding Protein / Q000502:physiology*
C577356:ARHGEF2 protein, human; D020662:Guanine Nucleotide Exchange Factors; D019012:Integrin beta1; D009363:Neoplasm Proteins; C107953:RAC1 protein, human; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; D006160:Guanosine Triphosphate; D020830:rac1 GTP-Binding Protein; D020743:rhoB GTP-Binding Protein