RanBPM, a novel interaction partner of the brain-specific protein p42IP4/centaurin alpha-1.

The protein p42(IP4) (aka Centaurin alpha-1) is highly enriched in the brain and has specific binding sites for the membrane lipid phosphatidylinositol 3,4,5-trisphosphate and the soluble messenger inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P(4); IP4). p42(IP4) shuttles between plasma membrane, cytosol and cell nucleus. However, the molecular function of p42(IP4) is still largely unclear. Here, we report a novel interaction partner for p42(IP4), Ran binding protein in microtubule-organizing center (RanBPM). RanBPM is ubiquitously expressed and seems to act as scaffolding and modulator protein. In our studies, we established this interaction in vitro and in vivo. The in vivo interaction was demonstrated with endogenous RanBPM from rat brain. Both proteins co-localize in transfected HEK 293 cells. We could show that the interaction does not require additional proteins. D-Ins(1,3,4,5)P(4), a specific ligand for p42(IP4), is a concentration-dependent and stereoselective inhibitor of this interaction; the l-isoform is much less effective. We found that mainly the SPRY domain of RanBPM mediates the p42(IP4)-RanBPM association. The ARFGAP domain of p42(IP4) is important for the interaction, without being the only interaction site. Recently, p42(IP4) and RanBPM were shown to be involved in dendritic differentiation. Thus, we hypothesize that RanBPM could act as a modulator together with p42(IP4) in synaptic plasticity.