Biomedical subjects

Zhao Ren

Publications and source records attributed to Zhao Ren.

3 recordsLinked to original sources

PubMed2003

Cell surface expression of GluR5 kainate receptors is regulated by an endoplasmic reticulum retention signal.

Kainate receptors (KARs) are mediators of excitatory neurotransmission in the mammalian central nervous system, and their efficient targeting and trafficking is critical for normal synaptic function. A key step in the delivery of KARs to the neuronal plasma membrane is the exit of newly assembled receptors from the endoplasmic reticulum (ER). Here we report the identification of a novel ER retention signal in the alternatively spliced C-terminal domain of the GluR5-2b subunit, which controls receptor trafficking in both heterologous cells and neurons. The ER retention motif consists of a critical arginine (Arg-896) and surrounding amino acids, disruption of which promotes ER exit and surface expression of the receptors, as well as altering their physiological properties. The Arg-896-mediated ER retention of GluR5 is regulated by a mutation that mimics phosphorylation of Thr-898, but not by PDZ interactions. Furthermore, two positively charged residues (Arg-900 and Lys-901) in the C terminus were also found to regulate ER export of the receptors. Taken together, our results identify novel trafficking signals in the C-terminal domain of GluR5-2b and demonstrate that alternative splicing is an important mechanism regulating KAR function.

Alternative Splicing↗

PubMed2003

Multiple trafficking signals regulate kainate receptor KA2 subunit surface expression.

The kainate receptor subunit KA2 does not form functional homomeric channels despite its structural similarity to the functional glutamate receptor 5-7subunits and high agonist binding affinity in in vitro assays. In this study, we first demonstrate that homomeric KA2 receptors fail to reach the plasma membrane and then identify the molecular mechanisms preventing surface expression. Specifically, we show that KA2 subunits form homooligomeric receptors that are confined to the endoplasmic reticulum (ER). We then demonstrate that, in both heterologous expression systems and primary neurons, the intracellular retention of KA2 is not caused by subunit misfolding but, rather, is mediated through discrete protein trafficking signals, including an arginine-rich ER retention/retrieval motif and a di-leucine endocytic sequence in the C terminus of the KA2 subunit. Disruption of these motifs results in ER exit and surface expression of KA2 homomeric receptors that remain nonfunctional. Furthermore, our data suggest that the ER retention/retrieval signal in KA2 is sterically shielded during heteromeric assembly, allowing delivery of functional heteromeric receptors to the plasma membrane. Taken together, our results illustrate novel regulatory mechanisms that control the intracellular trafficking and surface expression of kainate receptors.

Amino Acid Motifs↗

PubMedDate not supplied

Real-time determination of microbial activity of pasteurized fluid milk using a novel microrespirometer method.

The effectiveness of the rapid CO2 evolution rate (CER) method was evaluated by using a novel noninstrumental microrespirometer to determine the microbial activity of pasteurized milk and comparing it with traditional culturing methods in homogeneous milk samples. Three different kinds of milk (skim, 1% fat, and whole) stored at 2 temperatures (4 degrees and 7 degrees C) were measured daily for CER, aerobic plate count (APC), and psychrotrophic bacterial count. The mean initial rates of CO2 evolution for all 3 samples stored at the 2 temperatures ranged from 3.42 to 3.71 microL/h/mL and increased to 29 microL/h/mL and above on the final day of the experiment. Regression analysis showed a high correlation (R = 0.98-0.99) between the APC and CER results in combined milk samples. A cut-off value of CER (25 microL/h/mL) for milk spoilage at refrigeration temperatures was identified. The real-time CER method shows promise as a potential alternative to the traditional culture method.

Animals↗