This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this proposal is to understand better the molecular and cellular mechanism of the functional roles of dopamine receptor interacting proteins in the dopaminergic neuronal development and pathophysiology of neurodegenerative diseases. Abnormal activity of the dopamine system has been implicated in psychological and neurological disorders. The regulatory roles of dopamine receptors have been suggested in neuronal development by numerous studies of dopamine receptor expressions during different stages of brain development. The D2 dopamine receptor selective agonist was shown to increase neurite outgrowth in cultured rat cortical neurons. However, the mechanisms and factors of signaling pathways of dopamine receptors underlying the development of dopaminergic neurons and pathophysiology of neurodegenerative diseases still remain to be elucidated. In order to understand better the cellular and molecular mechanism of signaling pathways of the dopamine receptors we chose to study the D2 dopamine receptor (DAR) and its interacting proteins. We used the yeast two-hybrid assay to identify the interacting proteins of D2 DAR from rat brain cDNA library. One of the D2 DAR interacting proteins was atypical protein kinase c zeta interacting protein (ZIP). The interaction between D2 DAR and ZIP was confirmed biochemically and immunohistochemically. The expression of D2 DAR in the membrane was reduced when both D2 DAR and ZIP were co-expressed in cultured cells suggesting that ZIP impairs the trafficking of D2 DAR. In this proposal, we confirm the functional interaction between D2 DAR and ZIP in catecholaminergic cell line.
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