p62 serves as a shuttling factor for TrkA interaction with the proteasome.
p62 serves as a shuttling factor for TrkA interaction with the proteasome.
复制标题
DOI：
10.1016/j.bbrc.2008.06.082
复制
发表时间：
2008-09-12
影响因子：
3.1
通讯作者：
Wooten, Marie W.
中科院分区：
文献类型：
--
作者：
Geetha, Thangiah;Seibenhener, M. Lamar;Chen, Li;Madura, Kiran;Wooten, Marie W.
支架蛋白p62参与TrkA的内化和运输。该受体在被溶酶体降解之前被蛋白酶体去泛素化。在这里，我们证明了p62作为泛素化的TrkA与Rpt1相互作用的穿梭蛋白，Rpt1是26S蛋白酶体19S调节颗粒的六个ATPase之一。在p62−/−小鼠中，脑TrkA不能与Rpt1相互作用。在从p62−/−脑中分离的蛋白酶体中，trkA与Rpt1的相互作用减少，但可通过加入p62而恢复。P62的UBA结构域与TrkA相互作用，其PB1/UBL域与Rpt1的C-末端区域的AAA-ATPase盒相互作用。最后，神经营养素依赖的TrkA的转换因p62水平降低而受损。这些发现表明，p62作为泛素化底物与蛋白酶体相互作用的穿梭因子，可以促进神经元中局部的蛋白质周转。
The scaffold protein p62 is involved in internalization and trafficking of TrkA. The receptor is deubiquitinated by the proteasomes prior to degradation by lysosomes. Here we demonstrate that p62 serves as a shuttling protein for interaction of ubiquitinated TrkA with Rpt1, one of the six ATPases of 19S regulatory particle of the 26S proteasome. In p62 −/− mouse brain TrkA failed to interact with the Rpt1. The interaction of TrkA with Rpt1 was reduced in proteasomes isolated from p62 −/− brain, but was restored by addition of p62. The UBA domain of p62 interacts with TrkA and its PB1/UbL domain with AAA-ATPase cassette in the C-terminal region of Rpt1. Last, neurotrophin dependent turnover of TrkA was impaired by reduction in the level of p62. These findings reveal that p62 serves as a shuttling factor for interaction of ubiquitinated substrates with the proteasome and could promote localized protein turnover in neurons.
登录
查看更多内容
影响因子：
5.3
作者：
Clarke, DJ;Mondesert, G;Reed, SI
通讯作者：
Reed, SI
影响因子：
4.8
作者：
Lamark, T;Perander, M;Johansen, T
通讯作者：
Johansen, T
影响因子：
4.8
作者：
Hirano, Y;Yoshinaga, S;Inagaki, F
通讯作者：
Inagaki, F
影响因子：
5.3
作者：
Chuang, SM;Chen, L;Madura, M
通讯作者：
Madura, M
影响因子：
64.8
作者：
Bingol, Baris;Schuman, Erin M.
通讯作者：
Schuman, Erin M.