UCR Researchers Discover Single Protein Adgrl2 Dual-Regulates Brain Synapses and Blood-Brain Barrier Integrity

UCR study reveals how Adgrl2 protein uses alternative splicing to organize neural connections and stabilize the blood-brain barrier.

By: AXL Media

Published: Apr 28, 2026, 5:56 AM EDT

Source: Information for this report was sourced from University of California - Riverside

The Molecular Architect of Neural and Vascular Networks

The developing brain relies on two simultaneous construction projects: the creation of a vast communication network through neural synapses and the establishment of a robust life-support system via blood vessels. Researchers at UC Riverside have discovered that a single protein, Adgrl2, serves as the primary molecular guide for both. By helping cells recognize one another, Adgrl2 ensures that neurons partner up to form effective contact points for signal transmission. Assistant Professor Garret R. Anderson and his team found that this protein is not merely a structural component but a sophisticated director that manages the distinct needs of the brain's circuitry and its plumbing.

Alternative Splicing and the Art of Cellular Editing

The central mystery of the study was how one protein could perform vastly different roles in different cell types. The team, led by graduate student Alexander King, determined that the secret lies in a process known as alternative splicing. Although the genetic code for Adgrl2 is identical across the brain, individual cells edit these instructions before protein synthesis. This allows neurons to produce a version of the protein optimized for synaptic organization, while endothelial cells—which line the brain's blood vessels—create a variation designed to maintain vascular integrity and seal the blood-brain barrier.

Consequences of Vascular Integrity Failure

To test the necessity of Adgrl2 in the vascular system, the UCR team conducted experiments on mice where the protein was specifically removed from endothelial cells. The results demonstrated a total loss of vascular integrity, turning the normally selective blood-brain barrier into a "leaky" sieve. This failure allowed potentially harmful chemicals from the bloodstream to come into direct contact with sensitive neurons. Anderson noted that without the correct endothelial version of Adgrl2, the specialized units that protect the brain from systemic toxins cannot form, highlighting the protein's essential role in maintaining a healthy internal environment.