title: Adaptor protein XB130 is a Rac-controlled component of lamellipodia that regulates cell motility and invasion.
abstract: XB130 is a newly described cytosolic adaptor protein and tyrosine kinase substrate, involved in Src- and RET/PTC-dependent signaling. Although XB130 has been cloned as a homologue of actin-filament-associated protein (AFAP-110), its potential regulation by the actin skeleton and its putative roles in cytoskeleton regulation have not been addressed. Here, we show that XB130 (in contrast to AFAP-110) exhibited robust translocation to the cell periphery in response to various stimuli (including epidermal growth factor, wounding and expression of constitutively active Rac) that elicit lamellipodium formation. In stimulated cells, XB130 localized to the lamellipodial F-actin meshwork. Genetic and pharmacological data suggest that the key trigger for XB130 recruitment is the formation of the branched F-actin itself. Structure-function analysis revealed that both the XB130 N-terminus (167 amino acids) and C-terminus (63 amino acids) harbor crucial regions for its translocation to lamellipodia, whereas the PH domains and Src-targeted tyrosines are dispensable. Importantly, in TPC1 thyroid papillary carcinoma cells, silencing endogenous XB130 decreased the rate of wound closure, inhibited matrigel invasion, reduced lamellipodial persistence and slowed down spreading. Thus, XB130 is a novel Rac- and cytoskeleton-regulated and cytoskeleton-regulating adaptor protein that exhibits high affinity to lamellipodial (branched) F-actin and impacts motility and invasiveness of tumor cells.
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Monika
authors.initials: M
authors.lastname: Lodyga
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Bai
authors.forename: András
authors.initials: A
authors.lastname: Kapus
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D011554:Pseudopodia / Q000235:genetics / Q000378:metabolism*; D051381:Rats
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D051057:Proto-Oncogene Proteins c-akt