title: Concerted modulation of paxillin dynamics at focal adhesions by Deleted in Liver Cancer-1 and focal adhesion kinase during early cell spreading.
abstract: Deleted in Liver Cancer-1 (DLC1) is a RhoGTPase-activating protein (GAP) and a tumor suppressor often downregulated in cancers. It is localized to the focal adhesions (FAs) and its absence leads to enhanced cell migration, invasion, and metastasis. Although DLC1 interacts with focal adhesion kinase (FAK), talin, and tensin, its role in focal adhesions dynamics remains unclear. We examined the effect of DLC1 in Human Foreskin Fibroblasts and determined its localization, dynamics and impact on paxillin by Fluorescence Recovery After Photobleaching at both nascent and mature focal adhesions. During early cell spreading, DLC1 is preferentially localized at the inner/mature adhesions whereas phosphorylated paxillin occupies the outer/nascent FAs. In addition, DLC1 downregulates paxillin turnover in a process, that does not require its GAP activity. Instead, it requires the presence of FAK. Acting in concert, both DLC1 and FAK could provide a unique spatio-temporal mechanism to regulate paxillin function in tissue homeostasis.
authors.affiliation: Cell Signaling and Developmental Biology Laboratory, Department of Biological Sciences, National University of Singapore, Singapore; Mechanobiology Institute, National University of Singapore, Singapore.
authors.forename: Shelly
authors.initials: S
authors.lastname: Kaushik
authors.forename: Archna
authors.initials: A
authors.lastname: Ravi
authors.forename: Feroz M
authors.initials: FM
authors.lastname: Hameed
authors.forename: Boon Chuan
authors.initials: BC
authors.lastname: Low
mesh_terms: D002465:Cell Movement / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D051419:Paxillin / Q000378:metabolism*; D038761:Photobleaching; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: C112352:DLC1 protein, human; D020690:GTPase-Activating Proteins; C496061:PXN protein, human; D051419:Paxillin; D025521:Tumor Suppressor Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: GTPase activating protein (GAP); RhoGTPases; cell dynamics; tumor suppressor