Formin-like 1 (FMNL1) Is Regulated by N-terminal Myristoylation and Induces Polarized Membrane Blebbing
Formin-like 1 (FMNL1) Is Regulated by N-terminal Myristoylation and Induces Polarized Membrane Blebbing
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DOI：
10.1074/jbc.m109.060699
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发表时间：
2009-11-27
影响因子：
4.8
通讯作者：
Krackhardt, Angela M.
中科院分区：
文献类型：
--
作者：
Han, Yanyan;Eppinger, Elfriede;Krackhardt, Angela M.
FMNL 1在造血谱系来源的细胞中高度限制性表达，并且先前已被鉴定为肿瘤相关抗原。然而，FMNL 1的功能和调节并不明确。我们已经确定了一种新的剪接变异体（FMNL 1 γ）含有一个内含子保留在C末端影响透明的自抑制结构域（DAD）。FMNL 1 γ在多种细胞系中特异性地位于细胞膜和皮质。在缺乏DAD结构域的突变体（FMNL 1 Delta DAD）中观察到FMNL 1的类似定位，这表明在FMNL 1 γ中自抑制的失调是有效的。FMNL 1 γ和FMNL 1 δ DAD的表达诱导极化的非凋亡性起泡，其依赖于FMNL 1的N-末端肉豆蔻酰化，但不依赖于Src和ROCK活性。因此，我们的研究结果描述了N-肉豆蔻酰化作为FMNL 1的调节机制，FMNL 1负责膜运输，可能参与造血谱系衍生细胞的极化过程的多样性。
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 (FMNL1 gamma) containing an intron retention at the C terminus affecting the diaphanous autoinhibitory domain (DAD). FMNL1 gamma 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 (FMNL1 Delta DAD), indicating that deregulation of autoinhibition is effective in FMNL1 gamma. Expression of both FMNL1 gamma and FMNL1 Delta DAD 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.