%0 Journal Article %1 korsRegulatingPeroxisomeERContacts2022 %A Kors, Suzan %A Hacker, Christian %A Bolton, Chloe %A Maier, Renate %A Reimann, Lena %A Kitchener, Emily J. A. %A Warscheid, Bettina %A Costello, Joseph L. %A Schrader, Michael %C United States %D 2022 %J The Journal of cell biology %K 3 Acid Adaptor Binding,to_read,Vesicular Kinase Line,Endoplasmic Motifs,Animals,Cell Proteins Proteins/*chemistry/genetics/*metabolism,Mice,Mutation/genetics,Peroxisomes/*metabolism/ultrastructure,Phosphorylation,Phosphoserine/metabolism,Protein Proteins/*metabolism Reticulum/*metabolism/ultrastructure,Glycogen Signal Synthase Transducing/*chemistry/genetics/*metabolism,Amino Transport beta/*metabolism,Humans,Membrane %N 3 %R 10.1083/jcb.202003143 %T Regulating Peroxisome-ER Contacts via the ACBD5-VAPB Tether by FFAT Motif Phosphorylation and GSK3$\beta$. %V 221 %X Peroxisomes and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism. They form membrane contacts through interaction of the peroxisomal membrane protein ACBD5 (acyl-coenzyme A-binding domain protein 5) and the ER-resident protein VAPB (vesicle-associated membrane protein-associated protein B). ACBD5 binds to the major sperm protein domain of VAPB via its FFAT-like (two phenylalanines FF in an acidic tract) motif. However, molecular mechanisms, which regulate formation of these membrane contact sites, are unknown. Here, we reveal that peroxisome-ER associations via the ACBD5-VAPB tether are regulated by phosphorylation. We show that ACBD5-VAPB binding is phosphatase-sensitive and identify phosphorylation sites in the flanking regions and core of the FFAT-like motif, which alter interaction with VAPB-and thus peroxisome-ER contact sites-differently. Moreover, we demonstrate that GSK3$\beta$ (glycogen synthase kinase-3 $\beta$) regulates this interaction. Our findings reveal for the first time a molecular mechanism for the regulation of peroxisome-ER contacts in mammalian cells and expand the current model of FFAT motifs and VAP interaction.

@article{korsRegulatingPeroxisomeERContacts2022, abstract = {Peroxisomes and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism. They form membrane contacts through interaction of the peroxisomal membrane protein ACBD5 (acyl-coenzyme A-binding domain protein 5) and the ER-resident protein VAPB (vesicle-associated membrane protein-associated protein B). ACBD5 binds to the major sperm protein domain of VAPB via its FFAT-like (two phenylalanines [FF] in an acidic tract) motif. However, molecular mechanisms, which regulate formation of these membrane contact sites, are unknown. Here, we reveal that peroxisome-ER associations via the ACBD5-VAPB tether are regulated by phosphorylation. We show that ACBD5-VAPB binding is phosphatase-sensitive and identify phosphorylation sites in the flanking regions and core of the FFAT-like motif, which alter interaction with VAPB-and thus peroxisome-ER contact sites-differently. Moreover, we demonstrate that GSK3{$\beta$} (glycogen synthase kinase-3 {$\beta$}) regulates this interaction. Our findings reveal for the first time a molecular mechanism for the regulation of peroxisome-ER contacts in mammalian cells and expand the current model of FFAT motifs and VAP interaction.}, added-at = {2024-05-17T13:01:35.000+0200}, address = {United States}, author = {Kors, Suzan and Hacker, Christian and Bolton, Chloe and Maier, Renate and Reimann, Lena and Kitchener, Emily J. A. and Warscheid, Bettina and Costello, Joseph L. and Schrader, Michael}, biburl = {https://www.bibsonomy.org/bibtex/25be286092f478be5de622d655af0aebd/warscheidlab}, copyright = {{\copyright} 2022 Kors et al.}, doi = {10.1083/jcb.202003143}, interhash = {7c6b573844dc4dcd059ce2ff8f748900}, intrahash = {5be286092f478be5de622d655af0aebd}, issn = {1540-8140 0021-9525}, journal = {The Journal of cell biology}, keywords = {3 Acid Adaptor Binding,to_read,Vesicular Kinase Line,Endoplasmic Motifs,Animals,Cell Proteins Proteins/*chemistry/genetics/*metabolism,Mice,Mutation/genetics,Peroxisomes/*metabolism/ultrastructure,Phosphorylation,Phosphoserine/metabolism,Protein Proteins/*metabolism Reticulum/*metabolism/ultrastructure,Glycogen Signal Synthase Transducing/*chemistry/genetics/*metabolism,Amino Transport beta/*metabolism,Humans,Membrane}, langid = {english}, month = mar, number = 3, pmcid = {PMC8759595}, pmid = {35019937}, timestamp = {2024-05-17T13:01:35.000+0200}, title = {Regulating Peroxisome-{{ER}} Contacts via the {{ACBD5-VAPB}} Tether by {{FFAT}} Motif Phosphorylation and {{GSK3$\beta$}}.}, volume = 221, year = 2022 }