Trekking to the Tenure Finish Line: Teacher Educators and the Power of Peer Mentoring at an HBCU

The educator\u27s primary goal is to ensure student success by offering dynamic student experiences that will allow the students to synthesize their new learning with hopes of practical application. In higher education, a professor can easily fall into working in isolation due to the uniqueness of course offerings and areas of professional interest. However, when professors consciously build professional peer-mentoring relationships with colleagues that have similar interests and core values, both professors can grow. For example, when an experienced tenure track professor with K12 experience partners with a novice tenure track professor with over a decade of experience in education leadership, wonderful things can happen. This article details the first- and fifth-year experiences of two tenure track professors at an Historically Black College and University (HBCU) in the mid-Atlantic region. Instruction and scholarship, work-life balance, and relationships with students are areas of impact as an outcome of this peer-mentoring relationship

Dopamine receptor subtypes in renal brush border and basolateral membranes

Dopamine receptor subtypes in renal brush border and basolateral membranes. Dopamine (DA) modulates renal tubular sodium transport by actions at both brush border (BBM) and basolateral membranes (BLM). DA receptors have been demonstrated in proximal tubule but the subtype of DA receptor in either BBM or BLM has not been determined. DA-1 receptors were quantitated by the specific binding of 125I-SCH 23982, a DA-1 antagonist (defined by 20 µM SCH 23390, a DA-1 antagonist) and DA-2 receptors by the specific binding of 3H-methyl-spiroperidol or 3H-spiroperidol (defined by 30 µM trifluperidol, a predominantly DA-2 antagonist). The specific binding of 125I-SCH 23982 and 3H-methyl-spiroperidol or 3H-spiroperidol were saturable with time and ligand concentration and reversible. Analysis of Rosenthal plots by non-linear regression revealed a high affinity site and a very low affinity site for both BLM and BBM. Maximum receptor density was similar in BBM and BLM. Competition experiments with 125I-SCH 23982 revealed high and low affinity binding sites in both BBM and BLM. The high affinity site was characteristic of a DA-1 receptor. Competition experiments with 3H-spiroperidol were also suggestive of DA-2 receptors. DA-1 but not DA-2 drugs increased adenylate cyclase and phospholipase-C activities in both BBM and BLM. However, their effects were greater in BLM than BBM. We conclude that DA-1 and DA-2 receptors are present in both BBM and BLM in canine kidney. Renal DA-1 receptors are linked to stimulation of both adenylate cyclase and phospholipase-C activity

Dopamine D3 receptor inhibits the ubiquitin-specific peptidase 48 to promote NHE3 degradation

The dopamine D3 receptor (D3R) is crucial in the regulation of blood pressure and sodium balance, in that Drd3 gene ablation in mice results in hypertension and failure to excrete a dietary salt load. The mechanism responsible for the renal sodium retention in these mice is largely unknown. We now offer and describe a novel mechanism by which D3R decreases sodium transport in the long term by inhibiting the deubiquitinylating activity of ubiquitin-specific peptidase 48 (USP48), thereby promoting Na +-H+ exchanger (NHE)-3 degradation. We found that stimulation with the D3R-specific agonist PD128907 (1 μM, 30 min) promoted the interaction and colocalization among D3R, NHE3, and USP48; inhibited USP48 activity (-35±6%, vs. vehicle), resulting in increased ubiquitinylated NHE3 (-140±10%); and decreased NHE3 expression (-50±9%) in human renal proximal tubule cells (hRPTCs). USP48 silencing decreased NHE3\u27s half-life (USP48 siRNA t1/2=6.1 h vs. vehicle t 1/2=12.9 h), whereas overexpression of USP48 increased NHE3 half-life (t1/2=21.8 h), indicating that USP48 protects NHE3 from degradation via deubiquitinylation. USP48 accounted for ̃30% of the total deubiquitinylating activity in these cells. Extending our studies in vivo, we found that pharmacologic blockade of D3R via the D3R-specific antagonist GR103691 (1 μg/kg/min, 4 d) in C57Bl/6J mice increased renal NHE3 expression (+310±15%, vs. vehicle), whereas an innovative kidneyrestricted Usp48 silencing via siRNA (3 μg/d, 7 d) increased ubiquitinylated NHE3 (+250±30%, vs. controls), decreased total NHE3 (-23±2%), and lowered blood pressure (-24±2 mm Hg), compared with that in control mice that received either the vehicle or nonsilencing siRNA. Our data demonstrate a crucial role for the dynamic interaction between D 3R and USP48 in the regulation of NHE3 expression and function. © FASEB

Sorting nexin 1 loss results in D\u3csub\u3e5\u3c/sub\u3e dopamine receptor dysfunction in human renal proximal tubule cells and hypertension in mice

The peripheral dopaminergic system plays a crucial role in blood pressure regulation through its actions on renal hemodynamics and epithelial ion transport. The dopamine D5 receptor (D5R) interacts with sorting nexin 1 (SNX1), a protein involved in receptor retrieval from the trans-Golgi network. In this report, we elucidated the spatial, temporal, and functional significance of this interaction in human renal proximal tubule cells and HEK293 cells stably expressing human D5R and in mice. Silencing of SNX1 expression via RNAi resulted in the failure of D5R to internalize and bind GTP, blunting of the agonist-induced increase in cAMP production and decrease in sodium transport, and up-regulation of angiotensin II receptor expression, of which expression was previously shown to be negatively regulated by D5R. Moreover, siRNA-mediated depletion of renal SNX1 in C57BL/6J and BALB/cJ mice resulted in increased blood pressure and blunted natriuretic response to agonist in salt-loaded BALB/cJ mice. These data demonstrate a crucial role for SNX1 in D5R trafficking and that SNX1 depletion results in D5R dysfunction and thus may represent a novel mechanism for the pathogenesis of essential hypertension. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc