A model for regulation by SynGAP-α1 of binding of synaptic proteins to PDZ-domain 'Slots' in the postsynaptic density

SynGAP is a Ras/Rap GTPase-activating protein (GAP) that is a major constituent of postsynaptic densities (PSDs) from mammalian forebrain. Its α1 isoform binds to all three PDZ (PSD-95, Discs-large, ZO-1) domains of PSD-95, the principal PSD scaffold, and can occupy as many as 15% of these PDZ domains. We present evidence that synGAP-α1 regulates the composition of the PSD by restricting binding to the PDZ domains of PSD-95. We show that phosphorylation by Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII) and Polo-like kinase-2 (PLK2) decreases its affinity for the PDZ domains by several fold, which would free PDZ domains for occupancy by other proteins. Finally, we show that three critical postsynaptic signaling proteins that bind to the PDZ domains of PSD-95 are present in higher concentration in PSDs isolated from mice with a heterozygous deletion of synGAP

Binding of synGAP to PDZ Domains of PSD-95 is Regulated by Phosphorylation and Shapes the Composition of the Postsynaptic Density

SynGAP is a Ras/Rap GTPase-activating protein (GAP) present in high concentration in postsynaptic densities (PSDs) from mammalian forebrain where it binds to all three PDZ (PSD-95, Discs-large, ZO-1) domains of PSD-95. We show that phosphorylation of synGAP by Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII) decreases its affinity for the PDZ domains as much as 10-fold, measured by surface plasmon resonance. SynGAP is abundant enough in postsynaptic densities (PSDs) to occupy about one third of the PDZ domains of PSD-95. Therefore, we hypothesize that phosphorylation by CaMKII reduces synGAP′s ability to restrict binding of other proteins to the PDZ domains of PSD-95. We support this hypothesis by showing that three critical postsynaptic signaling proteins that bind to the PDZ domains of PSD-95 are present at a higher ratio to PSD-95 in PSDs isolated from synGAP heterozygous mice

A model for regulation by SynGAP-α1 of binding of synaptic proteins to PDZ-domain 'Slots' in the postsynaptic density

SynGAP is a Ras/Rap GTPase-activating protein (GAP) that is a major constituent of postsynaptic densities (PSDs) from mammalian forebrain. Its α1 isoform binds to all three PDZ (PSD-95, Discs-large, ZO-1) domains of PSD-95, the principal PSD scaffold, and can occupy as many as 15% of these PDZ domains. We present evidence that synGAP-α1 regulates the composition of the PSD by restricting binding to the PDZ domains of PSD-95. We show that phosphorylation by Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII) and Polo-like kinase-2 (PLK2) decreases its affinity for the PDZ domains by several fold, which would free PDZ domains for occupancy by other proteins. Finally, we show that three critical postsynaptic signaling proteins that bind to the PDZ domains of PSD-95 are present in higher concentration in PSDs isolated from mice with a heterozygous deletion of synGAP

The Plastic Surgery Learning Module: Improving Plastic Surgery Education for Medical Students

BackgroundMedical students receive limited exposure to the field of plastic surgery because most students will not rotate in plastic surgery, especially those at schools without dedicated plastic surgery residency programs. This study aimed to create and validate a plastic surgery learning module for medical students to dispel media-propagated myths and misrepresentation of the breadth of plastic surgery and equip students with referral-making capabilities.MethodsThe plastic surgery learning module was created using Articulate Storyline 360 (New York, N.Y.). Student participants were recruited from a single medical school across all four classes. Pre- and postmodule surveys were administered via Qualtrics (Provo, Utah). Scores were computed for the general surgical knowledge section and for each specialty referral question.ResultsTwelve students completed usability testing and edits were subsequently made to optimize the module. The module took on average 66 minutes to complete. Sixty-five students (19 MS1, 16 MS2, 15 MS3, 15 MS4) completed efficacy testing. In the premodule survey, students were nearly 100% accurate in identifying breast-related referrals, unlike pediatric/craniofacial (avg: 68%), reconstruction/microsurgery (avg: 64%), and hand/upper extremity (avg: 30%) referrals. Students of all classes exhibited significant improvement in all testing categories except for the breast category, with the most improvement in the hand referrals category. Prior exposure to plastic surgery (57%) correlated with higher premodule hand (P = 0.003) and breast/cosmetic (P = 0.01) referral scores.ConclusionThe plastic surgery learning module shows promise to be a comprehensive yet affordable and time-efficient tool for medical students to learn about basic surgical principles and the scope of plastic surgery

Evaluation and Treatment of Entrapped Peripheral Nerve Catheters: A Case Report and Review.

Methods to remove retained peripheral nerve catheters range from non-invasive techniques to open surgical procedures. This study reviews two cases requiring surgical intervention for catheter remnant removal after catheter breakage and presents a systematic review describing the diagnosis and treatment of retained perineural catheters. While still very rare, our case report and systematic review demonstrate that retained nerve catheters can occur as the result of kinking or knotting, but also from catheter breakage. We recommend risk mitigation strategies for providers placing or caring for patients with regional nerve catheters