JEWJITSU PEPTIDES: Research Roundup: aGPCR mechanisms, Drosophila seminal factors, and SCFE events with vosoritide

The first source is a review that critically examines activation models for adhesion G protein–coupled receptors (aGPCRs). It summarizes structural, functional and biophysical evidence indicating that the classical tethered agonist (TA) model does not fully explain aGPCR signaling in all contexts, especially for receptors that lack cleavage or operate under physiological forces. The authors describe an alternative extracellular region (ECR)–dependent mechanism in which conformational or allosteric changes in the ECR can modulate signaling independent of TA exposure and propose an integrated, context‑dependent framework that encompasses both modes.

The second source reports experimental work in Drosophila focusing on how the Hox gene Abdominal‑B shapes the male accessory gland and seminal transferome. Loss of Abdominal‑B expression in secondary cells of the iab‑6cocu enhancer mutant alters their transcriptional and secretory identity, reduces levels of specific seminal fluid proteins implicated in sperm binding and Sex Peptide network function, and abolishes the female long‑term post‑mating response. The study identifies two previously unreported Sex Peptide network proteins, Cornutus (CG1701) and Hanrej (CG42564), and links Cornutus to mating‑dependent dense core granule vesicle release.

The third source presents a case series from two investigator‑initiated, single‑center, open‑label phase II vosoritide trials in children with genetic short stature. Five participants developed slipped capital femoral epiphysis (SCFE), all after more than 12 months of treatment, and all presented with the valgus type. SCFE was observed in subsets of participants with Aggrecan (ACAN) mutations and with Turner syndrome in these cohorts, but not uniformly across other genetic subgroups. The authors note that vosoritide may be associated with higher SCFE risk in some conditions and emphasize that causal mechanisms, contributory factors and generalizability remain uncertain and require further study.