This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison Spring 2009
What does SORL1 interact with?
Since we've seen before how SORL1 acts a switch to sort APP into different metabolic pathways, I expected to see SORL1 interact with a good amount of proteins involved with lipid transport and metabolism. By searching for interactions in the String database I was able to visualizes an interaction network. The interaction network above was generated using all of the active prediction methods availabe on String (Co-expression, experiments, textmining, etc) and requiring a high level of confidence in the result. When you compare this to the interaction network below using the same parameters except only requiring medium confidence. From what we've learned about SORL1 already, the fact that APP and APOE are found to interact with SORL1 with high confidence is expected. However, it is interesting to see some of the proteins that I was unaware of that interact with SORL1.
GGA1 and GGA2 are ADP-ribosylation factor-binding proteins. According to GeneCards, GGA1 plays "a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (AC-LL) motif." Because we know that SORL1 helps mediate whether APP ends up in the recycling endosomal or late endosomal pathway, the interaction with GGA1 and GGA2 is one of high interest. Since the fundamental problem with Alzheimer's plaques is that proteins get sorted into the wrong pathways, the more that can be elucidated about this process, the better chance of developing a therapy.
In the Rogaeva paper that was reviewed earlier, the pathway that SORL1 is involved in includes Beta-secretase 1 precursor (BACE). According to GeneCards, the protein encoded by BACE is responsible for the proteolytic processing of APP by cleaving at the N-terminus between residues 671 and 672. Again we see that SORL1 interacts with a protein involved in the processing of APP. As was stated earlier, the details of these interactions may play a vital role in a more complete understanding of Alzheimer's Disease mechanisms.
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Last Updated 5/13/09
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