1. Human VAPome Analysis Reveals MOSPD1 and MOSPD3 as Membrane Contact Site Proteins Interacting with FFAT-Related FFNT Motifs.
- Author
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Cabukusta B, Berlin I, van Elsland DM, Forkink I, Spits M, de Jong AWM, Akkermans JJLL, Wijdeven RHM, Janssen GMC, van Veelen PA, and Neefjes J
- Subjects
- Amino Acid Motifs genetics, Cell Line, Cell Line, Tumor, Cell Membrane metabolism, Cell Membrane physiology, Endoplasmic Reticulum genetics, Endoplasmic Reticulum metabolism, Humans, Intracellular Signaling Peptides and Proteins physiology, Membrane Proteins physiology, Mitochondrial Membranes metabolism, Protein Binding genetics, Protein Interaction Domains and Motifs genetics, Protein Interaction Domains and Motifs physiology, Protein Interaction Mapping methods, Vesicular Transport Proteins physiology, Intracellular Signaling Peptides and Proteins metabolism, Membrane Proteins metabolism, Vesicular Transport Proteins metabolism
- Abstract
Membrane contact sites (MCS) are intracellular regions where two organelles come closer to exchange information and material. The majority of the endoplasmic reticulum (ER) MCS are attributed to the ER-localized tether proteins VAPA, VAPB, and MOSPD2. These recruit other proteins to the ER by interacting with their FFAT motifs. Here, we describe MOSPD1 and MOSPD3 as ER-localized tethers interacting with FFAT motif-containing proteins. Using BioID, we identify proteins interacting with VAP and MOSPD proteins and find that MOSPD1 and MOSPD3 prefer unconventional FFAT-related FFNT (two phenylalanines [FF] in a neutral tract) motifs. Moreover, VAPA/VAPB/MOSPD2 and MOSPD1/MOSPD3 assemble into two separate ER-resident complexes to interact with FFAT and FFNT motifs, respectively. Because of their ability to interact with FFNT motifs, MOSPD1 and MOSPD3 could form MCS between the ER and other organelles. Collectively, these findings expand the VAP family of proteins and highlight two separate complexes in control of interactions between intracellular compartments., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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