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Biomedical subjects

Linda Tran

Publications and source records attributed to Linda Tran.

3 recordsLinked to original sources

PTP1B-dependent insulin receptor phosphorylation/residency in the endocytic recycling compartment of CHO-IR cells.

Insulin binds to the alpha subunit of the insulin receptor (IR) on the cell surface. The insulin-IR complex is subsequently internalized and trafficked within the cell. Endocytosed receptors, devoid of insulin, recycle back to the plasma membrane through the endocytic recycling compartment (ERC). Using a high content screening system, we investigate the intracellular trafficking of the IR and its phosphorylation state, within the ERC, in response to protein tyrosine phosphatase-1B (PTP1B) inhibition. Insulin stimulates, in a time- and dose-dependent manner, the accumulation of phosphorylated IR (pY(1158,1162,1163 IR) in the ERC of CHO-IR cells. Treatment of CHO-IR cells with PTP1B-specific inhibitors or siRNA leads to dose-dependent increases in IR residency and phosphorylation within the ERC. The results also demonstrate that PTP1B redistributes within CHO-IR cells upon insulin challenge. The established system will allow for efficient screening of candidate inhibitors for the modulation of PTP1B activity.

Animals↗

How do we track invisible objects?

We previously demonstrated that observers in multiple object tracking experiments can successfully track targets when all the objects simultaneously vanish for periods lasting several hundred milliseconds (Alvarez, Horowitz, Arsenio, Dimase, and Wolfe, 2005). How do observers do this? Since observers can track objects that move behind occluders (e.g., Scholl and Pylyshyn, 1999), they may treat a temporal gap as a case of complete occlusion. If so, performance should improve if occlusion cues (deletion and accretion) are provided and items disappear and reappear one by one (asynchronously), rather than simultaneously. However, we found better performance with simultaneous than with asynchronous disappearance (Experiment 1), whereas occlusion cues were detrimental (Experiment 2). We propose that observers tolerate a gap in tracking by storing the current task state when objects vanish and resuming tracking on the basis of that memory when the objects reappear (a task-switching account).

Adolescent↗

Interaction of calcineurin and type-A GABA receptor gamma 2 subunits produces long-term depression at CA1 inhibitory synapses.

Long-term depression (LTD) is an activity-dependent weakening of synaptic efficacy at individual inhibitory synapses, a possible cellular model of learning and memory. Here, we show that the induction of LTD of inhibitory transmission recruits activated calcineurin (CaN) to dephosphorylate type-A GABA receptor (GABA(A)Rs) via the direct binding of CaN catalytic domain to the second intracellular domain of the GABA(A)R-gamma(2) subunits. Prevention of the CaN-GABA(A) receptor complex formation by expression of an autoinhibitory domain of CaN in the hippocampus of transgenic mice blocks the induction of LTD. Conversely, genetic expression of the CaN catalytic domain in the hippocampus depresses inhibitory synaptic responses, occluding LTD. Thus, an activity-dependent physical and functional interaction between CaN and GABA(A) receptors is both necessary and sufficient for inducing LTD at CA1 individual inhibitory synapses.

Animals↗