Marsman Marije, Jordens Ingrid, Rocha Nuno, Kuijl Coenraad, Janssen Lennert, Neefjes Jacques
Division of Tumor Biology, The Netherlands Cancer Institute, Amsterdam 1066CX, The Netherlands.
Biochem Biophys Res Commun. 2006 Jun 9;344(3):747-56. doi: 10.1016/j.bbrc.2006.03.178. Epub 2006 Apr 6.
The small GTPase Rab7 controls fusion and transport of late endocytic compartments. A critical mediator is the Rab7 effector RILP that recruits the minus-end dynein-dynactin motor complex to these compartments. We identified a natural occurring splice variant of RILP (RILPsv) lacking only 27 amino acids encoded by exon VII. Both variants bind Rab7, prolong its GTP-bound state, and induce clustering of late endocytic compartments. However, RILPsv does not recruit the dynein-dynactin complex, implicating exon VII in motor recruitment. Clustering might still occur via dimerization, since both RILP and RILPsv are able to form hetero- and homo-dimers. Moreover, both effectors compete for Rab7 binding but with different outcome for dynein-dynactin recruitment and transport. Hence, RILPsv provides an extra dimension to the control of vesicle fusion and transport by the small GTPase Rab7.
小GTP酶Rab7控制晚期内吞小室的融合与运输。一个关键的介导因子是Rab7效应蛋白RILP，它将负端动力蛋白-动力蛋白激活蛋白复合物招募到这些小室。我们鉴定出一种天然存在的RILP剪接变体（RILPsv），它仅缺少外显子VII编码的27个氨基酸。这两种变体都结合Rab7，延长其GTP结合状态，并诱导晚期内吞小室聚集。然而，RILPsv不招募动力蛋白-动力蛋白激活蛋白复合物，这表明外显子VII参与了马达蛋白招募。由于RILP和RILPsv都能够形成异源二聚体和同源二聚体，聚集仍可能通过二聚化发生。此外，这两种效应蛋白竞争Rab7结合，但对动力蛋白-动力蛋白激活蛋白招募和运输的结果不同。因此，RILPsv为小GTP酶Rab7对囊泡融合和运输的控制提供了一个额外的维度。
