Role of the obligate STRIPAK complex component Mob4 in zebrafish vascular development and stability

The STRiatin Interacting Phosphatases and Kinases (STRIPAK) complex is a conserved multiprotein module with functions in cell proliferation, cell growth, and cancer. Primarily examined through proteomic and in vitro studies, there is a relative lack of insight into the in vivo function of the STRIPAK complex during development. Motivated by the prominent interaction of STRIPAK and the CCM3 adapter protein, which is associated with the vascular disease cerebral cavernous malformation (CCM), we sought to examine the role of the conserved STRIPAK component Mob4 in early zebrafish vascular development. We use proximity-dependent biotinylation (BioID) coupled with mass spectrometry to show that Mob4 is a component of the STRIPAK complex in zebrafish. Loss of mob4 leads to pronounced cardiovascular and neuronal defects, including a leaky cerebral vasculature, hypersprouting of venous endothelial cells and poor neuronal branching. Conditional transgenic models further demonstrate a continuous and broad requirement for Mob4 in development. Taken together, these results suggest a key role for STRIPAK function in vascular development and stability, replicating hallmarks of CCM.