Lipid rafts are special microdomains on the cell plasma membrane, composed of a combination of sphingolipids, cholesterol, and membrane proteins. These specialized membranes mediate cellular processes by serving as organizing centers for the assembly of Homatropine Bromide signaling molecules, influencing membrane protein trafficking, and regulating neurotransmission. Many membranelocalized signaling pathways have been reported to depend on association with lipid rafts including those activated by EGF, IgE, the T- and B-cell receptors, and CD40-mediated Akt phosphorylation. A recent report showed a dynamic residence of the myeloid cell-specific adhesion GPCR EMR2 during signaling. In this study, we demonstrated that collagen III treatment causes a shift of GPR56C from non-raft to raft fractions, suggesting that GPR56 probably signals most efficiently in these nanodomains. In contrary to the previous report, we also observed a similar shift in L640R mutant receptors upon Octinoxate ligand stimulation. In vitro characterization of GPR56 indicates that various BFPPassociated mutations disrupt its function through different mechanisms. Mutations in the tip of GPR56N renders the receptor inactive by abolishing ligand binding, whereas mutations at the GPS motif within the GAIN domain disrupt receptor function by abolishing the GAIN domain-mediated receptor autocleavage. Previous biochemical studies have demonstrated that most disease-associated mutations reduce the surface expression of GPR56, with the exception of the L640R mutant that actually retains a high level of surface expression. This reinforces the reasoning that there are probably other mechanisms responsible for the null phenotype associated with this mutation. In this study, we discovered that L640R mutant receptor behaves very similarly to the wild type GPR56 except in regards to collagen III-mediated RhoA activation. As we did not directly measure collagen III binding to the L640R mutant, it is also formally possible that collagen III binding is compromised by this mutation, thereby blocking RhoA signal transduction. This seems implausible as collagen III treatment released GPR56N from the membrane-bound GPR56C as well as triggered a shift of GPR56C from non-DRM to DRM fractions in both wild type and L640R mutant GPR56. The L640 side chain faces the extracellular cavity, which is important for ligand interaction in the rhodopsin and secretin families of GPCRs. Amino acid sequence alignment revealed that L640 is evolutionarily conserved in GPR56, across multiple species, but not so in the majority of other adhesion GPCRs family members. Taken together, it is possible that the mutation of Leucine to an Arginine may interfere with the activation of the receptor by creating a locked inactive receptor. The long and charged side chain of arginine may reach out to residues from other transmembrane helices of the receptor and become involved in new interactions that favor an inactive receptor conformation, abolishing the signaling ability of the receptor. Alternatively, L640 could be critical for Ga12/13 docking to GPR56C, thereby rendering L640R incapable of signaling via RhoA. Gastric cancer is the second leading cause of cancer death worldwide. Single-agent chemotherapy for 
advanced gastric cancer includes capecitabine or 5-fluorouracil, while combination therapy includes cisplatin plus 5-fluorouracil or cisplatin plus capecitabine. Unfortunately, gastric cancer has shown low responsibility to chemotherapy.