Study On Lipid Metabolism Under The Regulation Of Nuclear Transport Factors Of C.Elegans By SREBPs

The Sterol Regulatory Element Binding Protein(SREBPs)is important nuclear transport factor in lipid metabolism which has a structure of basic helix-loop-helix leucine zipper.SREBPs has many functions including responding to the level of lipid,regulating the downstream factors of fat synthesis,taking part in fat synthesis,it can also participate in mTOR or carbohydrate metabolism and other signaling pathway.SREBPs is associated with obesity,fatty liver,type 2 diabetes,cardiovascular diseases and cancer.Therefore,SREBPs has a profound significance for disease prevention and treatment.At present,we have known the cleavage and activation of SREBPs from endoplasmic reticulum to Golgi body.However,how nSREBPs transports from cytoplasm to nucleus and how transcripts return to cytoplasm is still unknown.The research uses C.elegans to explore the nuclear transport of SREBPs,thereby to explore the role of SREBPs in lipid metabolism.Nuclear pore complex(NPC)provides a channel for material communication and transporting between cytoplasm and nucleus in nuclear membrane.Once the balance of NPC is broken,NPC cannot work normally.It will stop the transport,broke transcription and translation,affect the expression of downstream factors and disturb signaling pathway.Therefore,NPC is a channel to NPC maintains homeostasis between cytoplasm to nucleus and steady inheritance of genetic information.C.elegans is a model which has good conservative,simple structure,rapid reproduction and being suitable for large-scale screening.We use the SREBPs homologous genes sbp-1 in C.elegans to learn the transport of SREBPs.Firstly,we the possible factors which effect the transport of sbp-1,then,choosing the factors also influence fat content.We choose imb-3,ran-1,ran-4,xpo-1 as subjects after two rounds of screening.sbp-1 is the homologous gene of SREBPs in C.elegans and is highly conservative.imb-3,ran-1,ran-4,xpo-1 are factors to participate in material transport in NPC.When they are interfered,C.elegens body is small and white,no eggs,shortened lifespan.The transport of sbp-1 cannot carry out normally and the expression of downsterm genes fat-5,fat-6,fat-7 reduce.Lipid synthese and the contend of TAG reduce and SCDs activities are inhabited.In PC pathway,imb-3,ran-1,ran-4,xpo-1 RNAi inhabit the sbp-1 expression which induce by sams-1 RNAi.Exogenous addition of cholesterol,fat and sbp-1(ep79)content recovery that tell us there has other pathways involved in cholesterol metabolism.At the same time,the ER morphological change and the co-location of SBP-1 and HDEL reduce under imb-3,ran-1,ran-4,xpo-1 RNAi.We also obversed other nuclear transport factors including DAF-16,NHR-80,HLH-30.We found that ran-1 interferes all and imb-3,xpo-1,ran-4 have selectivity but the law has not been found.Altogether,imb-3,ran-1,ran-4,xpo-1 belong to nuclear transport factors,when they are interfered,affect lipid synthese and lifespan.They are relative to phospholipid,cholesterol,membrane and have different effects to transcription factors.They take part in sbp-1 in nuclear transport after cleavage activation and play an important role in lipid metabolism.