Adaptive Lipid Immiscibility and Membrane Remodeling Are Active Functional Determinants of Primary Ciliogenesis
Adaptive Lipid Immiscibility and Membrane Remodeling Are Active Functional Determinants of Primary Ciliogenesis
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DOI：
10.1002/smtd.202000711
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发表时间：
2020-12-16
期刊：
影响因子：
12.4
通讯作者：
Alonso, Miguel A.
中科院分区：
文献类型：
--
作者：
Bernabe-Rubio, Miguel;Bosch-Fortea, Minerva;Alonso, Miguel A.
在热力学平衡下，在模型膜和天然膜中观察到脂质液-液不溶性及其随之产生的横向异质性。然而，富含胆固醇的膜结构域，有时被称为脂筏，是很难观察时空活细胞。尽管它们在许多生物过程中很重要，但它们存在的有力证据仍然难以捉摸。这主要是由于难以同时确定它们的化学组成和物理化学性质，同时时空分辨它们的纳米畴寿命和分子动力学。在这项研究中，一个定制的方法的基础上超分辨率受激发射耗尽（STED）显微镜和光栅成像相关光谱（RICS）是用来克服这个问题。这种方法，激光交错共焦RICS和STED-RICS（LICSR），能够同时跟踪脂质横向包装和动态在纳米级。先前的工作表明，在极化的上皮细胞中，中间体残余许可证初级纤毛的形成通过一个未知的机制。LICSR表明，脂质的不可渗透性及其自适应的集体纳米级自组装是至关重要的中间体残留物提供浓缩膜的中心体的生物起源的睫状膜。因此，这项工作提出了突破性的脂质生物学领域提供了令人信服的证据，在初级纤毛发生液体有序样膜的功能作用。
Lipid liquid-liquid immiscibility and its consequent lateral heterogeneity have been observed under thermodynamic equilibrium in model and native membranes. However, cholesterol-rich membrane domains, sometimes referred to as lipid rafts, are difficult to observe spatiotemporally in live cells. Despite their importance in many biological processes, robust evidence for their existence remains elusive. This is mainly due to the difficulty in simultaneously determining their chemical composition and physicochemical nature, whilst spatiotemporally resolving their nanodomain lifetime and molecular dynamics. In this study, a bespoke method based on super-resolution stimulated emission depletion (STED) microscopy and raster imaging correlation spectroscopy (RICS) is used to overcome this issue. This methodology, laser interleaved confocal RICS and STED-RICS (LICSR), enables simultaneous tracking of lipid lateral packing and dynamics at the nanoscale. Previous work indicated that, in polarized epithelial cells, the midbody remnant licenses primary cilium formation through an unidentified mechanism. LICSR shows that lipid immiscibility and its adaptive collective nanoscale self-assembly are crucial for the midbody remnant to supply condensed membranes to the centrosome for the biogenesis of the ciliary membrane. Hence, this work poses a breakthrough in the field of lipid biology by providing compelling evidence of a functional role for liquid ordered-like membranes in primary ciliogenesis.