Targeting of Sna3p to the Endosomal Pathway Depends on Its Interaction with Rsp5p and Multivesicular Body Sorting on Its Ubiquitylation
Targeting of Sna3p to the Endosomal Pathway Depends on Its Interaction with Rsp5p and Multivesicular Body Sorting on Its Ubiquitylation
复制标题
Sna3p 靶向内体途径取决于其与 Rsp5p 的相互作用以及对其泛素化的多囊泡体分选
DOI：
--
复制
发表时间：
2007
期刊：
影响因子：
--
通讯作者：
P. Morsomme
中科院分区：
文献类型：
--
作者：
Marta Stawiecka;W. Pokrzywa;J. Morvan;T. Zoladek;R. Haguenauer‐Tsapis;D. Urban;P. Morsomme
Rsp 5 p是Nedd 4家族的泛素（Ub）-蛋白连接酶，其携带参与与含PPXY蛋白相互作用的WW结构域。它在细胞内运输的几个阶段起着关键作用，例如Ub介导的内吞货物的内化和Ub介导的膜蛋白分选到多泡体（MVB）的内囊泡，这是一个对它们随后靶向液泡腔至关重要的过程。Sna 3 p是一种膜蛋白，以前被描述为不依赖于Ub的MVB货物，但蛋白质组学研究表明它是一种泛素化蛋白。Sna 3 p带有PPXY基序。我们观察到，该基序介导其与Rsp 5 p WW结构域的相互作用。Sna 3 p PPXY基序或Rsp 5 p WW 3结构域的突变或Rsp 5量的减少导致Sna 3 p向多个移动的囊泡的错误定位，并阻止其向内体途径的分选。这种分选缺陷似乎发生在rsp 5突变体中由其他MVB货物显示的缺陷之前，这些货物被正确分选到内体途径，但错误分选到液泡膜而不是液泡腔。Sna 3 p在一个靶赖氨酸上被聚泛素化，并且缺乏其靶赖氨酸的突变体Sna 3 p显示缺陷的MVB分选。Sna 3 p经历Rsp 5依赖性多泛素化，具有K63连接的Ub链。
Rsp5p is an ubiquitin (Ub)‐protein ligase of the Nedd4 family that carries WW domains involved in interaction with PPXY‐containing proteins. It plays a key role at several stages of intracellular trafficking, such as Ub‐mediated internalization of endocytic cargoes and Ub‐mediated sorting of membrane proteins to internal vesicles of multivesicular bodies (MVBs), a process that is crucial for their subsequent targeting to the vacuolar lumen. Sna3p is a membrane protein previously described as an Ub‐independent MVB cargo, but proteomic studies have since shown it to be an ubiquitylated protein. Sna3p carries a PPXY motif. We observed that this motif mediates its interaction with Rsp5p WW domains. Mutation of either the Sna3p PPXY motif or the Rsp5p WW3 domain or reduction in the amounts of Rsp5 results in the mistargeting of Sna3p to multiple mobile vesicles and prevents its sorting to the endosomal pathway. This sorting defect appears to occur prior to the defect displayed in rsp5 mutants by other MVB cargoes, which are correctly sorted to the endosomal pathway but missorted to the vacuolar membrane instead of the vacuolar lumen. Sna3p is polyubiquitylated on one target lysine, and a mutant Sna3p lacking its target lysine displays defective MVB sorting. Sna3p undergoes Rsp5‐dependent polyubiquitylation, with K63‐linked Ub chains.
登录
查看更多内容
影响因子：
3.3
作者：
Katzmann, DJ;Sarkar, S;Emr, SD
通讯作者：
Emr, SD
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Ellison,MJ;Hochstrasser,M
通讯作者：
Hochstrasser,M
影响因子：
3.3
作者：
Oestreich, Andrea J.;Aboian, Mariam;Katzmann, David J.
通讯作者：
Katzmann, David J.
影响因子：
3.3
作者：
Swaminathan, S;Amerik, AY;Hochstrasser, M
通讯作者：
Hochstrasser, M
影响因子：
3.3
作者：
Pizzirusso, M;Chang, A
通讯作者：
Chang, A