The Endosomal Protein WDFY2 Suppress Autophagic Flux via VPS34 Methylation to Regulate Cellular Sene

来源 :The 7th International Symposium on Autophagy 2015(第七届自噬国际研讨会 | 被引量 : 0次 | 上传用户:boblllll
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
During autophagic process, autophagosomes carrying cellular cargoes fuse with lysosomes for degradation of damaged proteins and organelles.However, the molecular mechanism underlying autophagosome maturation is largely unknown.Here we report that WD domain and FYVE domain containing protein 2 (WDFY2), an early endosome protein, exhibited an inhibitory effect on autophagosome-lysosome fusion.Endogenous WDFY2 served as a signaling platform to recruit arginine methyltransferase PRMT5, by which in turn methylated Vps34.Methylation of Vps34 was required for its interaction with Rubicon, and leading to inhibition of autophagosomes maturation.Furthermore, MEF from WDFY2 knockout mice showed an acceleration of autophagic flux, which was well associated with cellular senescence.Our data reveal that WDFY2 is a negative regulator of autophagy by mediating a series of interactions among PRMT5, Vps34 and Rubicon.
其他文献
  Caveolin-1 (CAV1) is well known as a principle scaffolding protein of caveolae, a specialized plasma membrane structure.Relatively the caveolae-independent
  In selective autophagy, receptors are central for cargo selection and delivery.However, it remains yet unclear whether and how multiple autophagy receptors
  Macroautophagy is a catabolic pathway that targets large, long-lived structures such as protein aggregates, damaged organelles and invading pathogens to cel
  NRBF2 (Nuclear receptor binding factor 2), a stable component of Beclin1-VPS34 complex,modulates the VPS34 kinase activity and autophagy.NRBF2 function is h
In mammals, including humans, several diseases associated with elevated levels of γ-amino-butyric acid (GABA), the primary inhibitory neurotransmitter, have be
会议
  Autophagic clearance of misfolded or aggregated proteins is critical to protein quality control and cellular homeostasis.The underlying mechanism is not wel
  Autophagy transports cytosolic materials into lysosomes/vacuoles either in bulk or selectively.A prototype of selective autophagy, the budding yeast cytopla
  The endoplasmic reticulum (ER) is the largest intracellular endomembrane system enabling synthesis and transport of cellular components.Constant ER turnover
  The diversity of physiological processes associated to autophagy, such as cellular homeostasis,survival, differentiation, development and immunity led to th
  Autophagy is a homeostatic process whereby autophagosomes deliver cytoplasmic components and damaged organelles to lysosomes forming degradative autolysosom