title: Formin-like 1 (FMNL1) is regulated by N-terminal myristoylation and induces polarized membrane blebbing.
abstract: The formin protein formin-like 1 (FMNL1) is highly restrictedly expressed in hematopoietic lineage-derived cells and has been previously identified as a tumor-associated antigen. However, function and regulation of FMNL1 are not well defined. We have identified a novel splice variant (FMNL1gamma) containing an intron retention at the C terminus affecting the diaphanous autoinhibitory domain (DAD). FMNL1gamma is specifically located at the cell membrane and cortex in diverse cell lines. Similar localization of FMNL1 was observed for a mutant lacking the DAD domain (FMNL1DeltaDAD), indicating that deregulation of autoinhibition is effective in FMNL1gamma. Expression of both FMNL1gamma and FMNL1DeltaDAD induces polarized nonapoptotic blebbing that is dependent on N-terminal myristoylation of FMNL1 but independent of Src and ROCK activity. Thus, our results describe N-myristoylation as a regulative mechanism of FMNL1 responsible for membrane trafficking potentially involved in a diversity of polarized processes of hematopoietic lineage-derived cells.
authors.affiliation: Helmholtz Zentrum München, National Research Center for Environment and Health, Institute of Molecular Immunology, Marchioninistrasse 25, 81377 Munich, Germany.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Han
authors.forename: Elfriede
authors.initials: E
authors.lastname: Eppinger
authors.forename: Ingrid G
authors.initials: IG
authors.lastname: Schuster
authors.forename: Luise U
authors.initials: LU
authors.lastname: Weigand
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liang
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Christian
authors.initials: C
authors.lastname: Peschel
authors.forename: Angela M
authors.initials: AM
authors.lastname: Krackhardt
mesh_terms: D017398:Alternative Splicing; D001665:Binding Sites; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D000080865:Formins; D006801:Humans; D015151:Immunoblotting; D020014:K562 Cells; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009154:Mutation; D019814:Myristic Acid / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D054460:rho-Associated Kinases / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; C476204:FMNL1 protein, human; D000080865:Formins; D020033:Protein Isoforms; D019814:Myristic Acid; D019061:src-Family Kinases; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases