Formin 1-isoform IV deficient cells exhibit defects in cell spreading and focal adhesion formation.
BACKGROUND
Regulation of the cytoskeleton is a central feature of cell migration. The formin family of proteins controls the rate of actin nucleation at its barbed end. Thus, formins are predicted to contribute to several important cell processes such as locomotion, membrane ruffling, vesicle endocytosis, and stress fiber formation and disassociation.


RESULTS
In this study we investigated the functional role of Formin1-isoform4 (Fmn1-IV) by using genetically null primary cells that displayed augmented protrusive behaviour during wound healing and delayed cell spreading. Cells deficient of Fmn1-IV also showed reduced efficiency of focal adhesion formation. Additionally, we generated an enhanced green fluorescence protein (EGFP)-fused Fmn1-IV knock-in mouse to monitor the endogenous subcellular localization of Fmn1-IV. Its localization was found within the cytoplasm and along microtubules, yet it was largely excluded from adherens junctions.


CONCLUSIONS
It was determined that Fmn1-IV, as an actin nucleator, contributes to protrusion of the cell's leading edge and focal adhesion formation, thus contributing to cell motility.
Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
Markus
M
Dettenhofer
Fen
F
Zhou
Philip
P
Leder
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D017931:DNA Primers; D005326:Fetal Proteins / Q000235:genetics / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D000080865:Formins; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology*; D008854:Microscopy, Electron; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D049452:Green Fluorescent Proteins