VAPA at the inner nuclear membrane affects nuclear lamins and nuclear morphology

Vesicle-associated membrane protein-associated protein A (VAPA) is a protein of the endoplasmic reticulum (ER) and a component of several membrane contact sites (MCSs). We show here that VAPA also localizes to the inner nuclear membrane (INM), in close proximity to nuclear lamins, INM proteins and nucleoporins. Using our proteomics approach 'rapamycin- and APEX-dependent identification of proteins by SILAC' (RAPIDS), we identified several nuclear proximity partners of VAPA, including emerin, different LAP2 isoforms, lamin A/C and Nup153. Depletion of VAPA in various cellular systems resulted in reduced nuclear lamin levels and aberrant nuclear morphology, including the formation of membrane invaginations and tunnels. Furthermore, histone acetylation levels were altered. Our data suggest that VAPA has distinct nuclear functions, in addition to its established role as an ER organizer.