Formin-like 1 (FMNL1) is regulated by N-terminal myristoylation and induces polarized membrane blebbing.
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.
Han
Yanyan
Y
Helmholtz Zentrum München, National Research Center for Environment and Health, Institute of Molecular Immunology, Marchioninistrasse 25, 81377 Munich, Germany.
Eppinger
Elfriede
E
Schuster
Ingrid G
IG
Weigand
Luise U
LU
Liang
Xiaoling
X
Kremmer
Elisabeth
E
Peschel
Christian
C
Krackhardt
Angela M
AM
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
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