Neumann Andrew, Sampath Revathi, Han Ke-Jun, Prekeris Rytis
Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States.
MicroPubl Biol. 2025 Jun 9;2025. doi: 10.17912/micropub.biology.001629. eCollection 2025.
The Rap family of GTPases are emerging as major regulators of actin dynamics and cell migration. However, how Rap GTPases are activated and targeted to their subcellular localization remains to be fully understood. Recent work has shown that Rab40/CRL5-dependent mono-ubiquitylation is required for Rap2 activation. Here, we show that Rap1 is also mono-ubiquitylated by a Rab40/CRL5 E3 ubiquitin ligase complex and that Rap1 mono-ubiquitylation is necessary for Rap1 localization to both the plasma membrane and nuclear envelope. In summary, this work shows that Rab40/CRL5 is a major regulator of the activity and spatiotemporal dynamics of the Rap family of GTPases.
GTP酶的Rap家族正逐渐成为肌动蛋白动力学和细胞迁移的主要调节因子。然而，Rap GTP酶如何被激活以及靶向其亚细胞定位仍有待充分了解。最近的研究表明，Rap2激活需要Rab40/CRL5依赖性单泛素化。在此，我们表明Rap1也被Rab40/CRL5 E3泛素连接酶复合物单泛素化，并且Rap1单泛素化对于Rap1定位于质膜和核膜都是必需的。总之，这项工作表明Rab40/CRL5是GTP酶Rap家族活性和时空动力学的主要调节因子。
