Sequestosome 1 is part of the interaction network of VAPB

VAPB (Vesicle-Associated-membrane Protein-associated proteins B) is a tail-anchored mem-brane protein of the endoplasmic reticulum that can also be detected at the inner nuclear mem-brane. As a component of many contact sites between the endoplasmic reticulum and other or-ganelles, VAPB is engaged in multiple protein interactions with a plethora of binding partners. A mutant version of VAPB, P56S-VAPB, that results from a single point mutation is involved in a familial form of amyotrophic lateral sclerosis (ALS8). We performed RAPIDS (rapamycin- and APEX-dependent identification of proteins by SILAC) to identify proteins that interact with or are in close proximity to P56S-VAPB. The mutation abrogates the interaction of VAPB with many known binding partners. Instead, Sequestosome 1 (SQSTM1) was identified as a major in-teraction/proximity partner, a protein that is known as an autophagic adapter. Remarkably, not only the mutant P56S-VAPB, but also the wild type protein interacts with SQSTM1, as shown by proximity ligation assays and co-immunoprecipiation experiments.