Serotonin and its 14 cognate receptors have been well-characterized over the years, yet the data produces a confusing picture regarding their functionality. To large extent, the functional attributes of the receptors apparently depend upon the specific cell type in which they are expressed. This study is designed to characterize the role of serotonin and several different responding receptors in the stimulation and regulation of lymphocytes. Our preliminary data has established the presence of serotonin in this system and show that the receptors are functionally active. Pharmacological anomalies with the 5-HT 1A receptor have led us to the discovery of a novel chimeric mRNA that encodes a putative fusion protein containing the first third of the 1A protein. Based on our preliminary data three specific aims are proposed that are designed to fundamentally characterize the serotonin pathways in lymphocytes.
The first aim i s intended to explore whether serotonin is an autocrine survival factor in neoplastic lymphocytes and to expand our knowledge of the role of serotonin in the activation and differentiation of primary naive helper T cells.
The second aim of the proposal is intended to functionally characterize the novel 1A-fusion transcript identified in the lymphocytes. The last aim of the proposal is designed to address the mechanism of action of the serotonergic signals that are transduced through its cognate receptors. For this aim, we will dissect the relevant signal transduction pathways associated with the 5-HT 1B receptor in a T cell line and in primary T cells. Basically, this proposal is designed to explore the role of serotonin (a neurotransmitter, well-known for its involvement in the control of emotional responses) in mounting immune responses. We hypothesize that serotonin is a critical regulator of the immune system. Understanding the nature and role of the serotonergic receptors in the immune system may lead to the advent of new therapeutic strategies to combat autoimmune disease and treat the problems associated with transplant rejection.
|Tao, Zhihua; Ghosh, Gourisankar (2012) Understanding NIK regulation from its structure. Structure 20:1615-7|