Fatty links between multisystem proteinopathy and Small VCP-Interacting Protein
Ramzan, F.; Abrar, F.; Kumar, A.; Liao, L. M. Q.; Campbell, Z. E.; Gray, R. V.; Akanni, O.; Guyn, C. M.; Martin, D. D. O.
Show abstract
Multisystem proteinopathy (MSP) is a rare dominantly-inherited disorder that includes a cluster of diseases, including frontotemporal dementia, inclusion body myopathy, and Pagets disease of bone. MSP is caused by mutations in the gene encoding Valosin-Containing Protein (VCP). Patients with the same mutation, even within the same family, can present with a different combination of any or all of the above diseases, along with amyotrophic lateral sclerosis (ALS). The pleiotropic effects may be linked to the greater than 50 VCP cofactors that direct VCPs many roles in the cell. Small VCP-Interacting Protein (SVIP) is a small protein that directs VCP to autophagosomes and lysosomes. We found that SVIP directs VCP localization to autophagosomes in an acylation-dependent manner. We demonstrate that SVIP is myristoylated at glycine 2 and palmitoylated at cysteines 4 and 7. Acylation of SVIP is required to mediate cell death in the presence of the MSP-associated VCP variant (R155H-VCP), whereas blocking SVIP myristoylation prevents cytotoxicity. Therefore, SVIP acylation may present a novel target in MSP.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- α-Synuclein facilitates endocytosis by elevating the steady-state levels of phosphatidylinositol 4,5-bisphosphate 95%
- ALG-2 And Peflin Stimulate or Inhibit COPII Targeting And Secretion In Response To Calcium Signaling 95%
- Lipid-specific protein oligomerization is regulated by two interfaces in Marburg virus matrix protein VP40 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.