Wang Huajin, Becuwe Michel, Housden Benjamin E, Chitraju Chandramohan, Porras Ashley J, Graham Morven M, Liu Xinran N, Thiam Abdou Rachid, Savage David B, Agarwal Anil K, Garg Abhimanyu, Olarte Maria-Jesus, Lin Qingqing, Fröhlich Florian, Hannibal-Bach Hans Kristian, Upadhyayula Srigokul, Perrimon Norbert, Kirchhausen Tomas, Ejsing Christer S, Walther Tobias C, Farese Robert V
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, United States.
Department of Genetics and Complex Diseases, Harvard T H Chan School of Public Health, Boston, United States.
Elife. 2016 Aug 26;5:e16582. doi: 10.7554/eLife.16582.
How proteins control the biogenesis of cellular lipid droplets (LDs) is poorly understood. Using and human cells, we show here that seipin, an ER protein implicated in LD biology, mediates a discrete step in LD formation-the conversion of small, nascent LDs to larger, mature LDs. Seipin forms discrete and dynamic foci in the ER that interact with nascent LDs to enable their growth. In the absence of seipin, numerous small, nascent LDs accumulate near the ER and most often fail to grow. Those that do grow prematurely acquire lipid synthesis enzymes and undergo expansion, eventually leading to the giant LDs characteristic of seipin deficiency. Our studies identify a discrete step of LD formation, namely the conversion of nascent LDs to mature LDs, and define a molecular role for seipin in this process, most likely by acting at ER-LD contact sites to enable lipid transfer to nascent LDs.
蛋白质如何控制细胞脂滴（LDs）的生物合成目前还知之甚少。利用[具体实验对象未提及]和人类细胞，我们在此表明，丝氨酸磷酸酶（seipin），一种与LD生物学相关的内质网（ER）蛋白，介导了LD形成过程中的一个离散步骤——将小的新生LDs转化为更大的成熟LDs。丝氨酸磷酸酶在内质网中形成离散且动态的焦点，与新生LDs相互作用以促进其生长。在没有丝氨酸磷酸酶的情况下，大量小的新生LDs在内质网附近积累，并且大多数情况下无法生长。那些确实生长的LDs会过早获得脂质合成酶并进行扩张，最终导致丝氨酸磷酸酶缺乏所特有的巨大LDs。我们的研究确定了LD形成的一个离散步骤，即新生LDs向成熟LDs的转化，并定义了丝氨酸磷酸酶在此过程中的分子作用，最有可能是通过在内质网-LD接触位点发挥作用，使脂质转移到新生LDs上。
