Back to Search
Start Over
Focal adhesion-localization of START-GAP1/DLC1 is essential for cell motility and morphology
- Source :
- Genes to Cells. 14:227-241
- Publication Year :
- 2009
- Publisher :
- Wiley, 2009.
-
Abstract
- There is a class of GTPase activating proteins for the Rho family GTPases (RhoGAPs) that contain the steroidogenic acute regulatory protein (STAR)-related lipid transfer (START) domain. In mammals three genes encode such proteins and they are designated START-GAP1-3 or deleted in liver cancer 1-3 (DLC1-3). In this study, we examined the intracellular localization and roles of START-GAP1/DLC1 in cell motility. Immunofluorescence microscopic analysis of NRK cells and HeLa cells revealed that START-GAP1 was localized in focal adhesions. Amino acid residues 265-459 of START-GAP1 were found to be necessary for focal adhesion targeting and we name the region "the focal adhesion-targeting (FAT) domain." It was previously known that ectopic expression of START-GAP1 induced cell rounding. We demonstrated that the FAT domain of START-GAP1 was partially required for this morphological change. Furthermore, expression of this domain in HeLa cells resulted in dissociation of endogenous START-GAP1 from focal adhesions as a dominant negative modulator, reducing cell migration and spreading. Taken together, START-GAP1 is targeted to focal adhesions via the FAT domain and regulates actin rearrangement through down-regulation of active RhoA and Cdc42. Its absence from focal adhesions could, therefore, cause abnormal cell motility and spreading.
- Subjects :
- RHOA
Role of cell adhesions in neural development
PTK2
CDC42
Transfection
Models, Biological
Focal adhesion
Cell Movement
Genetics
Humans
Tissue Distribution
cdc42 GTP-Binding Protein
Cell Shape
Cells, Cultured
Paxillin
Focal Adhesions
biology
Tumor Suppressor Proteins
GTPase-Activating Proteins
Cell Biology
Protein Structure, Tertiary
Cell biology
Testin
biology.protein
DLC1
rhoA GTP-Binding Protein
HeLa Cells
Subjects
Details
- ISSN :
- 13652443 and 13569597
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Genes to Cells
- Accession number :
- edsair.doi.dedup.....ffc32b57c7fa52370a42e04ac89977c3