Membrane curvature regulates the spatial distribution of bulky glycoproteins.
Membrane curvature regulates the spatial distribution of bulky glycoproteins.
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DOI：
10.1038/s41467-022-30610-2
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发表时间：
2022-06-02
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
糖萼是分布在几乎所有细胞类型的细胞表面上的高度糖基化的蛋白质和脂质的外壳。最近，已经发现大的跨膜糖蛋白如MUC1可以通过诱导膜突起来调节膜形状。在这项工作中，我们研究了膜形状如何影响MUC1在细胞膜上的空间分布及其生物学意义的相互关系。通过采用纳米图案化的表面和膜雕刻蛋白质来操纵膜曲率，我们表明MUC1避免了正弯曲的膜（膜内陷），并在负弯曲的膜（膜突起）上积累。MUC1的曲率敏感性取决于其胞外域糖基化的长度和程度，大的和高度糖基化的形式优先远离正曲率。有趣的是，MUC1对正膜曲率的避免使其能够逃避内吞作用并从细胞膜上去除。这些发现还表明，MUC1胞外域的截短，经常在乳腺癌和卵巢癌中观察到，可能会增强其内吞作用，并加强其细胞内积累和信号传导。MUC1是细胞表面上的高度糖基化的蛋白质。在这里，作者表明MUC1由于其庞大的尺寸而偏好负膜曲率而不是正膜曲率，使得MUC1能够避免基于曲率偏好的内吞作用和表面去除。
The glycocalyx is a shell of heavily glycosylated proteins and lipids distributed on the cell surface of nearly all cell types. Recently, it has been found that bulky transmembrane glycoproteins such as MUC1 can modulate membrane shape by inducing membrane protrusions. In this work, we examine the reciprocal relationship of how membrane shape affects MUC1’s spatial distribution on the cell membrane and its biological significance. By employing nanopatterned surfaces and membrane-sculpting proteins to manipulate membrane curvature, we show that MUC1 avoids positively-curved membranes (membrane invaginations) and accumulates on negatively-curved membranes (membrane protrusions). MUC1’s curvature sensitivity is dependent on the length and the extent of glycosylation of its ectodomain, with large and highly glycosylated forms preferentially staying out of positive curvature. Interestingly, MUC1’s avoidance of positive membrane curvature enables it to escape from endocytosis and being removed from the cell membrane. These findings also suggest that the truncation of MUC1’s ectodomain, often observed in breast and ovarian cancers, may enhance its endocytosis and potentiate its intracellular accumulation and signaling. MUC1 is a heavily glycosylated protein on the cell surface. Here the authors show that MUC1 prefers negative over positive membrane curvature due to its bulky size, enabling MUC1 to avoid endocytosis and surface removal based on curvature preference.
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DOI：
10.1016/j.bbrc.2009.08.059
发表时间：
2009-10-30
影响因子：
3.1
作者：
Hisatsune, Akinori;Kawasaki, Mitsuru;Kim, Kwang Chul
通讯作者：
Kim, Kwang Chul
影响因子：
19
作者：
Diz-Muñoz A;Fletcher DA;Weiner OD
通讯作者：
Weiner OD
DOI：
10.1126/science.1223012
发表时间：
2012-08-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Button B;Cai LH;Ehre C;Kesimer M;Hill DB;Sheehan JK;Boucher RC;Rubinstein M
通讯作者：
Rubinstein M
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
DOI：
10.1111/j.1432-1033.1995.607_2.x
发表时间：
1995-10-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
BROCKHAUSEN, I;YANG, JM;TAYLORPAPADIMITRIOU, J
通讯作者：
TAYLORPAPADIMITRIOU, J