Formin-like 1 (FMNL1) Is Regulated by N-terminal Myristoylation and Induces Polarized Membrane Blebbing

• Published in: The Journal of biological chemistry 2009-11, Vol.284 (48), p.33409-33417
• Main Authors: Han, Yanyan, Eppinger, Elfriede, Schuster, Ingrid G., Weigand, Luise U., Liang, Xiaoling, Kremmer, Elisabeth, Peschel, Christian, Krackhardt, Angela M.
• Format: Article
• Language: English
• Subjects: Alternative Splicing; Binding Sites; Cell Line; Cell Line, Tumor; Cell Membrane - metabolism; Cells, Cultured; Cloning, Molecular; Cytoskeletal Proteins - chemistry; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; DNA, Complementary - chemistry; DNA, Complementary - genetics; Formins; Humans; Immunoblotting; K562 Cells; Membrane Transport, Structure, Function, and Biogenesis; Microscopy, Confocal; Molecular Sequence Data; Mutation; Myristic Acid - metabolism; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein Transport; Reverse Transcriptase Polymerase Chain Reaction; rho-Associated Kinases - metabolism; Sequence Analysis, DNA; src-Family Kinases - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109.060699

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 (FMNL1γ) containing an intron retention at the C terminus affecting the diaphanous autoinhibitory domain (DAD). FMNL1γ 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 (FMNL1ΔDAD), indicating that deregulation of autoinhibition is effective in FMNL1γ. Expression of both FMNL1γ and FMNL1ΔDAD 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.