ANKRD22 is an N-myristoylated hairpin-like monotopic membrane protein specifically localized to lipid droplets.
ANKRD22 is an N-myristoylated hairpin-like monotopic membrane protein specifically localized to lipid droplets.
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DOI：
10.1038/s41598-021-98486-8
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发表时间：
2021-09-28
影响因子：
4.6
通讯作者：
Moriya K
中科院分区：
文献类型：
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作者：
Utsumi T;Hosokawa T;Shichita M;Nishiue M;Iwamoto N;Harada H;Kiwado A;Yano M;Otsuka M;Moriya K
对 ANKRD22 的膜拓扑结构和细胞内定位进行了检查，ANKRD22 是一种新型人类 N-肉豆蔻酰化蛋白，具有预测的单次跨膜结构域，最近有报道称其在癌症中过度表达。对转染编码 ANKRD22 的 cDNA 和细胞器标记物的 COS-1 细胞进行免疫荧光染色，结果显示 ANKRD22 特异性定位于脂滴 (LD)。对 C 端与糖基化肿瘤坏死因子 (GLCTNF) 融合的 ANKRD22 突变体的细胞内定位进行分析，并评估其对蛋白质 N-糖基化的敏感性，结果表明 ANKRD22 在内质网 (ER) 膜上合成为 N-肉豆蔻酰化发夹样单位膜蛋白 氨基末端和羧基末端面向细胞质，然后分选至 LD。发现位于预测膜结构域中心的 Pro98 对于 ANKRD22 发夹状单位拓扑的形成至关重要。此外，发夹状单位拓扑和位于 C 末端附近的带正电残基被证明是 ANKRD22 从 ER 到 LD 的排序所必需的。发现蛋白质 N-肉豆蔻酰化对 LD 定位有积极影响。因此，多种因素，包括发夹样单位膜拓扑结构、C端带正电荷的残基和蛋白质N-肉豆蔻酰化协同影响ANKRD22对LD的细胞内靶向。
The membrane topology and intracellular localization of ANKRD22, a novel human N-myristoylated protein with a predicted single-pass transmembrane domain that was recently reported to be overexpressed in cancer, were examined. Immunofluorescence staining of COS-1 cells transfected with cDNA encoding ANKRD22 coupled with organelle markers revealed that ANKRD22 localized specifically to lipid droplets (LD). Analysis of the intracellular localization of ANKRD22 mutants C-terminally fused to glycosylatable tumor necrosis factor (GLCTNF) and assessment of their susceptibility to protein N-glycosylation revealed that ANKRD22 is synthesized on the endoplasmic reticulum (ER) membrane as an N-myristoylated hairpin-like monotopic membrane protein with the amino- and carboxyl termini facing the cytoplasm and then sorted to LD. Pro98 located at the center of the predicted membrane domain was found to be essential for the formation of the hairpin-like monotopic topology of ANKRD22. Moreover, the hairpin-like monotopic topology, and positively charged residues located near the C-terminus were demonstrated to be required for the sorting of ANKRD22 from ER to LD. Protein N-myristoylation was found to positively affect the LD localization. Thus, multiple factors, including hairpin-like monotopic membrane topology, C-terminal positively charged residues, and protein N-myristoylation cooperatively affected the intracellular targeting of ANKRD22 to LD.
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影响因子：
4.8
作者：
Kozjak, V;Wiedemann, N;Pfanner, N
通讯作者：
Pfanner, N
影响因子：
4.6
作者：
Kinoshita-Kikuta E;Utsumi T;Miyazaki A;Tokumoto C;Doi K;Harada H;Kinoshita E;Koike T
通讯作者：
Koike T
DOI：
10.1073/pnas.1423026112
发表时间：
2015-01-13
影响因子：
11.1
作者：
Chen, Shuliang;Desai, Tanvi;Novick, Peter J.
通讯作者：
Novick, Peter J.
影响因子：
7.8
作者：
Colombo, S;Longhi, R;Borgese, N
通讯作者：
Borgese, N
影响因子：
64.8
作者：
通讯作者：
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