mlck-peptide and 2-aminoethoxydiphenyl-borate

There are two major forms of long-term depression (LTD) of synaptic transmission in the central nervous system that require activation of either N-methyl-D-aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). In synapses in the perirhinal cortex, we have directly compared the Ca(2+) signaling mechanisms involved in NMDAR-LTD and mGluR-LTD. While both forms of LTD involve Ca(2+) release from intracellular stores, the Ca(2+) sensors involved are different; NMDAR-LTD involves calmodulin, while mGluR-LTD involves the neuronal Ca(2+) sensor (NCS) protein NCS-1. In addition, there is a specific requirement for IP3 and PKC, as well as protein interacting with C kinase (PICK-1) in mGluR-LTD. NCS-1 binds directly to PICK1 via its BAR domain in a Ca(2+)-dependent manner. Furthermore, the NCS-1-PICK1 association is stimulated by activation of mGluRs, but not NMDARs, and introduction of a PICK1 BAR domain fusion protein specifically blocks mGluR-LTD. Thus, NCS-1 plays a distinct role in mGluR-LTD.

Topics: Animals; Animals, Newborn; Boron Compounds; Calcium; Calcium Signaling; Carrier Proteins; Cell Cycle Proteins; Cells, Cultured; Cerebral Cortex; Chelating Agents; Dose-Response Relationship, Drug; Egtazic Acid; Electric Stimulation; Enzyme Inhibitors; Excitatory Amino Acid Agents; Immunoprecipitation; Long-Term Synaptic Depression; Neuronal Calcium-Sensor Proteins; Neurons; Neuropeptides; Nuclear Proteins; Organ Culture Techniques; Patch-Clamp Techniques; Peptides; Rats; Receptors, Metabotropic Glutamate; RNA Interference; RNA, Small Interfering; Transfection