van Vlijmen Thijs, Vleugel Mathijs, Evers Melvin, Mohammed Shabaz, Wulf Phebe S, Heck Albert J R, Hoogenraad Casper C, van der Sluijs Peter
Department of Cell Biology, University Medical Center Utrecht, Utrecht, The Netherlands.
FEBS Lett. 2008 Aug 20;582(19):2838-42. doi: 10.1016/j.febslet.2008.07.012. Epub 2008 Jul 14.
Exocytic events are tightly regulated cellular processes in which rab GTPases and their interacting proteins perform an important function. We set out to identify new binding partners of rab3, which mediates regulated secretion events in specialized cells. We discovered Zwint-1 as a rab3 specific binding protein that bound preferentially to rab3c. The interaction depends on a critical residue in rab3c that determines the binding efficiency of Zwint-1, which is immaterial for interaction with rabphilin3a. Rab3c and Zwint-1 are expressed highly in brain and colocalized extensively in primary hippocampal neurons. We also found that SNAP25 bound to the same region in Zwint-1 as rab3c, suggesting a new role for the kinetochore protein Zwint-1 in presynaptic events that are regulated by rab3 and SNAP25.
胞吐事件是受到严格调控的细胞过程，其中RAB GTP酶及其相互作用蛋白发挥着重要作用。我们着手鉴定RAB3的新结合伴侣，RAB3介导特殊细胞中的调节性分泌事件。我们发现Zwint-1是一种RAB3特异性结合蛋白，它优先与RAB3C结合。这种相互作用取决于RAB3C中的一个关键残基，该残基决定了Zwint-1的结合效率，而这对于与rabphilin3a的相互作用并不重要。RAB3C和Zwint-1在大脑中高度表达，并在原代海马神经元中广泛共定位。我们还发现，SNAP25与Zwint-1中与RAB3C相同的区域结合，这表明动粒蛋白Zwint-1在由RAB3和SNAP25调节的突触前事件中具有新作用。
