GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.
PMID:23790629
| Citation |
O'Sullivan, NC, Dräger, N and O'Kane, CJ (2013) Characterization of the Drosophila atlastin interactome reveals VCP as a functionally related interactor. J Genet Genomics 40:297-306 |
|---|---|
| Abstract |
At least 25 genes, many involved in trafficking, localisation or shaping of membrane organelles, have been identified as causative genes for the neurodegenerative disorder hereditary spastic paraplegia (HSP). One of the most commonly mutated HSP genes, atlastin-1, encodes a dynamin-like GTPase that mediates homotypic fusion of endoplasmic reticulum (ER) membranes. However, the molecular mechanisms of atlastin-1-related membrane fusion and axonopathy remain unclear. To better understand its mode of action, we used affinity purification coupled with mass spectrometry to identify protein interactors of atlastin in Drosophila. Analysis of 72 identified proteins revealed that the atlastin interactome contains many proteins involved in protein processing and transport, in addition to proteins with roles in mRNA binding, metabolism and mitochondrial proteins. The highest confidence interactor from mass spectrometry analysis, the ubiquitin-selective AAA-ATPase valosin-containing protein (VCP), was validated as an atlastin-interacting protein, and VCP and atlastin showed overlapping subcellular distributions. Furthermore, VCP acted as a genetic modifier of atlastin: loss of VCP partially suppressed an eye phenotype caused by atlastin overexpression, whereas overexpression of VCP enhanced this phenotype. These interactions between atlastin and VCP suggest a functional relationship between these two proteins, and point to potential shared mechanisms between HSP and other forms of neurodegeneration. |
| Links |
PubMed Online version:10.1016/j.jgg.2013.04.008 |
| Keywords |
|
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0046907: intracellular transport |
ECO:0000255: |
|
P |
Table 1.Valosin-containing protein (VCP) homologue function categorized by DAVID and receiving the highest MASCOT score in anti-myc affinity purification and mass-spectrometry with the protein atlastin. |
complete | |||
| GO:0016485: protein processing |
ECO:0000317: |
PMID:14597658[2] PMID:19131956[1] PMID:22641854[3]
|
P |
Fig. 1B. Proteins are identified through DAVID and again through DroPNet and constructed into a web through Cytoscape. Valosin-containing protein (VCP) homologue (TER94) is found in th protein processing section of the atlastin interactome web. |
complete | |||
| GO:0016485: protein processing |
ECO:0000316: |
UniProtKB:Q9VC57
|
P |
Fig. 2A. VCP is confirmed to interact with atlastin, known to function in protein processing, through co-immunoprecipitation. |
complete | |||
| GO:0007029: endoplasmic reticulum organization |
ECO:0000314: |
P |
Fig. 2B,C, and D all show atlastin and VCP in ER regions. |
complete | ||||
| GO:0016485: protein processing |
ECO:0000315: |
P |
Fig. 4. VCP contributes to atlastin function. VCP expression directly influences atlastin expression as seen by large or rough eyes. |
complete | ||||
| GO:0016485: protein processing |
ECO:0000314: |
P |
Fig. 5. Loss of VCP causes a suppression of the atlastin overexpression phenotype, rough or small eyes. |
complete | ||||
See also
References
See Help:References for how to manage references in GONUTS.
- ↑ 1.0 1.1 Huang, da W et al. (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4 44-57 PubMed GONUTS page
- ↑ Shannon, P et al. (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13 2498-504 PubMed GONUTS page
- ↑ Renaud, Y et al. (2012) DroPNet: a web portal for integrated analysis of Drosophila protein-protein interaction networks. Nucleic Acids Res. 40 W134-9 PubMed GONUTS page
