Nap1 regulates Dictyostelium cell motility and adhesion through SCAR-dependent and -independent pathways.
SCAR--also known as WAVE--is a key regulator of actin dynamics. Activation of SCAR enhances the nucleation of new actin filaments through the Arp2/3 complex, causing a localized increase in the rate of actin polymerization . In vivo, SCAR is held in a large regulatory complex, which includes PIR121 and Nap1 proteins, whose precise role is unclear. It was initially thought to hold SCAR inactive until needed , but recent data suggest that it is essential for SCAR function . Here, we show that disruption of the gene that encodes Nap1 (napA) causes loss of SCAR function. Cells lacking Nap1 are small and rounded, with diminished actin polymerization and small pseudopods. Furthermore, several aspects of the napA phenotype are more severe than those evoked by the absence of SCAR alone. In particular, napA mutants have defects in cell-substrate adhesion and multicellular development. Despite these defects, napA(-) cells move and chemotax surprisingly effectively. Our results show that the members of the complex have unexpectedly diverse biological roles.
School of Biosciences, University of Birmingham, Edgbaston, UK.
Neysi
N
Ibarra
Simone L
SL
Blagg
Francisca
F
Vazquez
Robert H
RH
Insall
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002630:Chemotactic Factors / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000166:cytology* / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D008840:Microfilament Proteins / Q000502:physiology*; D009154:Mutation; D010641:Phenotype; D015800:Protozoan Proteins / Q000235:genetics / Q000502:physiology*; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism
D002630:Chemotactic Factors; D008840:Microfilament Proteins; D015800:Protozoan Proteins; C491975:SCAR protein, Dictyostelium; D051300:Wiskott-Aldrich Syndrome Protein Family; D000242:Cyclic AMP