Formin-like 1 (FMNL1) Is Regulated by N-terminal Myristoylation and Induces Polarized Membrane Blebbing |
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| Authors: | Yanyan Han Elfriede Eppinger Ingrid G Schuster Luise U Weigand Xiaoling Liang Elisabeth Kremmer Christian Peschel and Angela M Krackhardt |
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| Institution: | From the ‡Helmholtz Zentrum München, National Research Center for Environment and Health, Institute of Molecular Immunology, Marchioninistrasse 25, 81377 Munich and ;the §III Medizinische Klinik, Klinikums Rechts der Isar, Technische Universität München, Ismaningerstrasse 15, 81675 Munich, Germany |
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| 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 (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. |
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