Ablation of ceramide synthase 2 strongly affects biophysical properties of membranes
Ablation of ceramide synthase 2 strongly affects biophysical properties of membranes
复制标题
DOI：
10.1194/jlr.m022715
复制
发表时间：
2012-03-01
影响因子：
6.5
通讯作者：
Futerman, Anthony H.
中科院分区：
文献类型：
--
作者：
Silva, Liana C.;Ben David, Oshrit;Futerman, Anthony H.
鞘脂（SL）酰基链结构和组成的改变对生物膜生物物理性能的影响尚不清楚。我们探索了从神经酰胺合成酶2 （CerS2）缺失小鼠分离的脂质部分制备的膜中消耗超长酰基链（VLC） SLs的生物物理后果，该小鼠无法合成C22-C24神经酰胺。我们证明，CerS2消融对肝脏和大脑有不同的影响，引起膜流动性的显著改变，并影响膜中存在的相的类型和/或程度。这些变化是VLC和不饱和SLs消耗的结果，在肝脏和大脑中发生的程度不同。此外，消融CerS2引起固有膜曲率的改变，导致强烈的形态学改变，促进囊泡粘附、膜融合和小管形成。总之，这些结果表明，vllc - sls的消耗强烈影响膜的生物物理特性，这可能会损害关键依赖于膜结构的细胞过程，如运输和分选。-席尔瓦，l.c.， O. Ben David， Y. Pewzner-Jung， E. L. Laviad， J. Stiban， S. Bandyopadhyay， A. H. Merrill, Jr.， M. Prieto， A. H. Futerman神经酰胺合酶2的消融强烈影响膜的生物物理特性。[j] .油脂杂志。2012。53: 430 - 436。
Little is known about the effects of altering sphingolipid (SL) acyl chain structure and composition on the biophysical properties of biological membranes. We explored the biophysical consequences of depleting very long acyl chain (VLC) SLs in membranes prepared from lipid fractions isolated from a ceramide synthase 2 (CerS2)-null mouse, which is unable to synthesize C22-C24 ceramides. We demonstrate that ablation of CerS2 has different effects on liver and brain, causing a significant alteration in the fluidity of the membrane and affecting the type and/or extent of the phases present in the membrane. These changes are a consequence of the depletion of VLC and unsaturated SLs, which occurs to a different extent in liver and brain. In addition, ablation of CerS2 causes changes in intrinsic membrane curvature, leading to strong morphological alterations that promote vesicle adhesion, membrane fusion, and tubule formation. Together, these results show that depletion of VLC-SLs strongly affects membrane biophysical properties, which may compromise cellular processes that critically depend on membrane structure, such as trafficking and sorting.-Silva, L. C., O. Ben David, Y. Pewzner-Jung, E. L. Laviad, J. Stiban, S. Bandyopadhyay, A. H. Merrill, Jr., M. Prieto, and A. H. Futerman. Ablation of ceramide synthase 2 strongly affects biophysical properties of membranes. J. Lipid Res. 2012. 53: 430-436.