Protein phosphatases at the nuclear envelope.

The nuclear envelope (NE) is a unique topological structure formed by lipid membranes (Inner and Outer Membrane: IM and OM) interrupted by open channels (Nuclear Pore complexes). Besides its well-established structural role in providing a physical separation between the genome and the cytoplasm and regulating the exchanges between the two cellular compartments, it has become quite evident in recent years that the NE also represents a hub for localized signal transduction. Mechanical, stress, or mitogen signals reach the nucleus and trigger the activation of several pathways, many effectors of which are processed at the NE. Therefore, the concept of the NE acting just as a barrier needs to be expanded to embrace all the dynamic processes that are indeed associated with it. In this context, dynamic protein association and turnover coupled to reversible post-translational modifications of NE components can provide important clues on how this integrated cellular machinery functions as a whole. Reversible protein phosphorylation is the most used mechanism to control protein dynamics and association in cells. Keys to the reversibility of the system are protein phosphatases and the regulation of their activity in space and time. As the NE is clearly becoming an interesting compartment for the control and transduction of several signalling pathways, in this review we will focus on the role of Protein Phosphatases at the NE since the significance of this class of proteins in this context has been little explored.