Helmholtz Zentrum München, National Research Center for Environment and Health, Institute of Molecular Immunology, Marchioninistrasse 25, 81377 Munich, Germany.
J Biol Chem. 2009 Nov 27;284(48):33409-17. doi: 10.1074/jbc.M109.060699. Epub 2009 Oct 8.
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.
formin 蛋白formin 样蛋白 1（FMNL1）在造血谱系衍生细胞中高度受限表达，先前已被鉴定为肿瘤相关抗原。然而，FMNL1 的功能和调节尚不清楚。我们已经鉴定出一种新型剪接变体（FMNL1gamma），其 C 末端存在内含子保留，影响 diaphanous 自动抑制结构域（DAD）。FMNL1gamma 特异性位于各种细胞系的细胞膜和皮质。对于缺乏 DAD 结构域的突变体（FMNL1DeltaDAD）也观察到类似的定位，表明 DAD 自动抑制的失调在 FMNL1gamma 中是有效的。表达 FMNL1gamma 和 FMNL1DeltaDAD 均可诱导极化的非凋亡起泡，这依赖于 FMNL1 的 N-端豆蔻酰化，但不依赖于Src 和 ROCK 活性。因此，我们的结果描述了 N-豆蔻酰化作为 FMNL1 的调节机制，负责膜运输，可能参与造血谱系衍生细胞的多种极化过程。
