Autism (NRCAM)

This web page was produced as an assignment for Gen677 at UW-Madison Spring 2009.

Neuronal cell adhesion molecule (NrCAM)

Figure 1. This is the predicted 3-D structure of the human NrCAM protein.  Retrieved from 
http://www.genecards.org/cgi-bin/carddisp.pl?gene=NRCAM

Search Tool for Retrieval of Interacting Genes/Proteins (STRING) 8.0

The STRING protein networks below show the protein interactions for NrCAM (Bravo in the networks).  These interactions are for the human protein only.  An interactive protein network can be accessed on the STRING website. The proteins in the networks below reinforce the Gene Ontology biological processes and functions that NrCAM is thought to play a role in. 

STRING Protein Interaction Net (evidence)

Figure 2.  NrCAM protein map from STRING based on evidence from a variety of sources. Note that Bravo is an alias for NrCAM in this protein network.  


From STRING 8.0, 2009. Bravo evidence map. Retrieved from
 http://string.embl.de/newstring
_cgi/show_network_section.pl. 

STRING Protein Interaction Net (confidence)

Figure 3. NrCAM protein map from STRING based on confidence of interactions between proteins.  Confidence in interaction is given by the boldness of the lines connecting the proteins. Note that Bravo is an alias for NrCAM in this protein network.


From STRING 8.0, 2009. Bravo confidence map. Retrieved from http://string.embl.de/newstring_
cgi/show_network_section.pl. 

OSPREY

I attempted to use Osprey to do similar interaction network analysis on NrCAM, however I was unable to unable to use the software for some reason. I hope to get this software working in order to verify and expand upon data from STRING. This analysis will be added as soon as it is available.

Analysis of interactions

STRING is a very good database for finding protein interactions due to the fact that it bases its scores on experimental evidence and protein interactions that are the most physiologically relevant.  Because I was not able to get the Osprey database to work, and MINT and BioCarta did not return any search results for NrCAM, I can only comment on the results from STRING.  Among the interacting proteins identified by STRING, the ANK2 and ANK3 proteins are of the greatest interest to me as the ankyrin binding function of NrCAM is supported by these interactions.  ANK2 and ANK3 are important in anchoring integral membrane proteins and other proteins to the cytoskeleton. Cytoskeletal maintenance is also a function of proteins that have FN3 domains which includes NrCAM. The activated leukocyte cell adhesion molecule (ALCAM) is also interesting as it may indicate that NrCAM is involved in the immune system which would be predicted based upon its I-set and Ig domains.  It would be interesting to look more into immune processes in autistic individuals, especially when the microarray data from the immune-resistant cancer cell experiments is considered.  LEF1 is also a protein worth looking into because of its expression in pre-B and T cells and its role in the Wnt signaling pathway.  These interactions have not been completely addressed beyond what is presented here, but I plan to look into the DNA motifs and protein domains of these interacting partners. This information will be valuable for future studies as it might provide new avenues in which NrCAM could be involved in autism.  

Drug Interactions: anti-psychotics, anti-depressants


Risperidone

Risperidone is an anti-psychotic medication often used to treat schizophrenia and bipolar disorder.  It is also used frequently to treat symptoms of autism including mania and episodes of depression.  It is also used to prevent dramatic mood swings in autistic individuals.

Image taken from: 
http://chembank.broad.harvard.edu/chemistry/
viewMolecule.htm?cbid=1795.  (retrieved 3/5/09)

Fluoxetine (Prozac)

Fluoxetine is an anti-depressant used to treat moderate to sever depression in autistic individuals.  It is used to maintain stable moods and interactions.

Image taken from:
http://chembank.broad.harvard.edu/chemistry/
viewMolecule.htm?cbid=1789. (retrieved 3/5/09)

Brett Maricque
[email protected]
Last updated: 5/13/2009
http://www.gen677.weebly.com