The Golgi-Associated PDZ Domain Protein Gopc/PIST Is Required for Synaptic Targeting of mGluR5

Abstract

In neuronal cells, many membrane receptors interact via their intracellular, C-terminal tails with PSD-95/discs large/ZO-1 (PDZ) domain proteins. Some PDZ proteins act as scaffold proteins. In addition, there are a few PDZ proteins such as Gopc which bind to receptors during intracellular transport. Gopc is localized at the trans-Golgi network (TGN) and binds to a variety of receptors, many of which are eventually targeted to postsynaptic sites. We have analyzed the role of Gopc by knockdown in primary cultured neurons and by generating a conditional Gopc knockout (KO) mouse line. In neurons, targeting of neuroligin 1 (Nlgn1) and metabotropic glutamate receptor 5 (mGlu5) to the plasma membrane was impaired upon depletion of Gopc, whereas NMDA receptors were not affected. In the hippocampus and cortex of Gopc KO animals, expression levels of Gopc-associated receptors were not altered, while their subcellular localization was disturbed. The targeting of mGlu5 to the postsynaptic density was reduced, coinciding with alterations in mGluR-dependent synaptic plasticity and deficiencies in a contextual fear conditioning paradigm. Our data imply Gopc in the correct subcellular sorting of its associated mGlu5 receptor in vivo.

Proteome Analysis of Alpine Merino Sheep Skin Reveals New Insights into the Mechanisms Involved in Regulating Wool Fiber Diameter

“…Previous studies suggest that these proteins are mainly involved in metabolic and signal transduction processes. CIDEA [46], CRYM [47], and MLX [48] regulate fat metabolism through different mechanisms, and GOPC [49] and CAMK2G [50] affect disease occurrence by participating in cell signal transduction. Currently, these proteins show a direct relationship to wool fiber diameter.…”

Group I Metabotropic Glutamate Receptors and Interacting Partners: An Update

“…By binding to mGlu5a, Gopc inhibited the ubiquitination and degradation of mGlu5a, resulting in an increase in the receptor expression [59] (Figure 2A). Conditional knockout of Gopc reduced the targeting of mGlu5 to the PSD in the mouse hippocampus [60]. Gopc deficiency also impaired mGlu1/5-ERK signaling in astroglial C6 cells, and overexpression of Gopc stabilized mGlu5 expression in the striatum in a rotenone-induced rat model of Parkinson's disease [61].…”

Role of Macrophage PIST Protein in Regulating Leishmania major Infection

“…In this context, it is important to note that several environmental cues and upstream regulators can induce autophagy by facilitating the assembly of the Beclin 1–Vps34 core complex, which is crucial for phagophore formation . One of these upstream autophagy regulators is PIST, also known as GOPC (Golgi-associated PDZ and coiled-coil motif-containing protein), which plays key roles in signal transduction pathways. − Additionally, PIST is involved in the intracellular trafficking of various cellular proteins, such as Cadherin 23, cystic fibrosis transmembrane conductance regulator (CFTR), and metabotropic glutamate receptor 5 (mGluR5). − …”