title: The multi-FERM-domain-containing protein FrmA is required for turnover of paxillin-adhesion sites during cell migration of Dictyostelium.
abstract: FERM domain proteins, including talins, ERMs, FAK and certain myosins, regulate connections between the plasma membrane, cytoskeleton and extracellular matrix. Here we show that FrmA, a Dictyostelium discoideum protein containing two talin-like FERM domains, plays a major role in normal cell shape, cell-substrate adhesion and actin cytoskeleton organisation. Using total internal reflection fluorescence (TIRF) microscopy we show that FrmA-null cells are more adherent to substrate than wild-type cells because of an increased number, persistence and mislocalisation of paxillin-rich cell-substrate adhesions, which is associated with decreased motility. We show for the first time that talinA colocalises with paxillin at the distal ends of filopodia to form cell-substrate adhesions and indeed arrives prior to paxillin. After a period of colocalisation, talin leaves the adhesion site followed by paxillin. Whereas talinA-rich spots turnover prior to the arrival of the main body of the cell, paxillin-rich spots turn over as the main body of the cell passes over it. In FrmA-null cells talinA initially localises to cell-substrate adhesion sites at the distal ends of filopodia but paxillin is instead localised to stabilised adhesion sites at the periphery of the main cell body. This suggests a model for cell-substrate adhesion in Dictyostelium whereby the talin-like FERM domains of FrmA regulate the temporal and spatial control of talinA and paxillin at cell-substrate adhesion sites, which in turn controls adhesion and motility.
authors: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK.
authors: Hitesh
authors: H
authors: Patel
authors: Ireen
authors: I
authors: König
authors: Masatsune
authors: M
authors: Tsujioka
authors: Margaret C
authors: MC
authors: Frame
authors: Kurt I
authors: KI
authors: Anderson
authors: Valerie G
authors: VG
authors: Brunton
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002465:Cell Movement; D017931:DNA Primers; D004023:Dictyostelium / Q000166:cytology*; D005455:Fluorescent Antibody Technique; D051419:Paxillin / Q000378:metabolism*; D015800:Protozoan Proteins / Q000502:physiology*
chemical_list: D000199:Actins; D017931:DNA Primers; D051419:Paxillin; D015800:Protozoan Proteins