Disease relevance of GOPC

• Modulation of mature cystic fibrosis transmembrane regulator protein by the PDZ domain protein CAL [1].
• The PDZ/coiled-coil domain containing protein PIST modulates insulin secretion in MIN6 insulinoma cells by interacting with somatostatin receptor subtype 5 [2].
• A patient, CAL, with gamma heavy chain disease is presented who has had a complete remission lasting over 2 yr with combination chemotherapy consisting of pulsatile cyclophosphamide and prednisone [3].
• Expression of the CAL cDNA in a melanoma cell line that was poorly adherent to laminin did not increase adhesion to laminin [4].

High impact information on GOPC

• Here we show that Golgi-associated PDZ- and coiled-coil motif-containing protein (GOPC), a recently identified Golgi-associated protein, is predominantly localized at the trans-Golgi region in round spermatids, and male mice in which GOPC has been disrupted are infertile with globozoospermia [5].
• Thus, GOPC provides important clues to understanding the mechanisms underlying spermatogenesis, and the GOPC-deficient mouse may be a unique and valuable model for human globozoospermia [5].
• Lack of acrosome formation in mice lacking a Golgi protein, GOPC [5].
• These data suggest that TC10 regulates both total and plasma membrane CFTR expression by interacting with CAL [6].
• Isoform-specific interaction of golgin-160 with the Golgi-associated protein PIST [7].

Biological context of GOPC

• In addition, PIST was demonstrated to be involved in autophagy and linked to processes of neurodegeneration [8].
• Molecular characters and morphological genetics of CAL gene in Chinese cabbage [9].
• Calsequestrin, a muscle calcium binding protein, has been shown to bind the extracellular matrix protein laminin and evidence has been presented that CAL (initially called aspartactin) is on the cell surface, consistent with a role as a laminin receptor (1) [4].

Anatomical context of GOPC

• These data reveal that CAL, a novel beta1AR-binding partner, modulates beta1AR intracellular trafficking, thereby revealing a new mechanism of regulation for beta1AR anterograde trafficking through the endoplasmic reticulum-Golgi complex to the plasma membrane [10].
• Golgin-160 and PIST colocalize to Golgi membranes and interact in vivo [7].
• The co-expression of hemagglutinin-tagged or Myc-tagged CAL with green fluorescent protein (GFP)-CFTR in COS-7 cells causes a dose-dependent reduction in mature GFP-CFTR, independent of its tags [1].
• Endogenous SSTR5 in the neuroendocrine AtT-20 tumor cell line is colocalized with PIST in the Golgi apparatus [11].
• Here, we show that PIST is expressed in pancreatic beta-cells and interacts with SSTR5 in these cells [2].

Associations of GOPC with chemical compounds

• Mutation of the terminal valine residue resulted in markedly reduced association of the beta1AR-CT with CAL [10].
• Interestingly, we also discovered a widely expressed isoform of golgin-160, golgin-160B, which lacks the exon encoding the leucine repeat that mediates binding to PIST [7].
• Importantly, bafilomycin A1 reverses CAL-mediated CFTR degradation [1].
• Glutathione S-transferase binding experiments identified an internal region of PIST that includes a coiled-coil domain, which interacts directly with golgin-160 [7].
• CAL is located primarily at the Golgi apparatus, co-localizing with trans-Golgi markers and is sensitive to Brefeldin A treatment [12].

Physical interactions of GOPC

• The PDZ domain of CAL binds to the C terminus of CFTR [12].
• The multi-domain protein PIST (protein interacting specifically with Tc10) interacts with the SSTR5 (somatostatin receptor 5) and is responsible for its intracellular localization [2].
• Here, we report that a Rho family small GTPase TC10 interacts with CAL [6].

Regulatory relationships of GOPC

• Co-expression of CAL enhances the degradation of CFTR [1].
• MIN6 cells over-expressing PIST display enhanced glucose-stimulated insulin secretion and a decreased sensitivity to SST-induced inhibition of insulin secretion [2].

Other interactions of GOPC

• PIST expression in MIN6 insulinoma cells is reduced by somatostatin (SST) [2].
• Using chemical shift perturbation experiments, we further studied the binding properties of the GOPC PDZ domain with the C-terminal motif of neuroligin [13].
• On the basis of NMR relaxation data, the alpha2 helix as well as the beta2-beta3 loop of CAL PDZ domain undergoes rapid dynamics [14].
• In immunofluorescence analyses, Rhotekin and PIST were suggested to co-localize at synapses in rat primary cultured hippocampal neurons [15].
• These results suggest a possible yet unidentified role of Rhotekin, in harmony with PIST and beta-catenin, in neuronal cells [15].

Analytical, diagnostic and therapeutic context of GOPC

• In cells, full-length beta1AR robustly associates with CAL, and this interaction is abolished by mutation of the terminal valine to alanine of the receptor (V477A), as determined by co-immunoprecipitation experiments and immunofluorescence co-localization studies [10].
• Immunoprecipitation experiments suggest that CAL exists as a multimer [12].

References