Latrophilin refers to a type of protein found on the outer surface of cells throughout the body. These proteins belong to a group known as adhesion G protein-coupled receptors, or GPCRs. Adhesion GPCRs have a unique structure with an elongated extracellular region and a seven-transmembrane domain. This arrangement allows latrophilins to serve dual purposes: participating in cell-to-cell adhesion and transmitting signals across the cell membrane.
The Black Widow Connection
The name “latrophilin” originates from its interaction with alpha-latrotoxin, a potent neurotoxin produced by black widow spiders (Latrodectus genus). This neurotoxin is the primary component in the spider’s venom that affects vertebrates. The discovery of latrophilin was directly linked to studying how this venom works, as researchers used alpha-latrotoxin to isolate the protein from brain tissue.
Alpha-latrotoxin binds to latrophilin-1 on presynaptic nerve endings. This binding triggers a dramatic and uncontrolled influx of calcium ions into the presynaptic membranes. The sudden surge of calcium then leads to a massive and unregulated release of neurotransmitters, disrupting normal nerve communication. While the toxin can also form pores in cell membranes, some research has used modified forms of the toxin that act solely through latrophilin-1 without creating these pores.
Functions in the Nervous System
Latrophilins perform a dual function within the nervous system, acting as both adhesion molecules and signaling receptors. As adhesion molecules, they help neurons and other cells stick together, maintaining tissue structure. They also function as receptors, receiving messages from the extracellular environment and relaying them into the cell.
Latrophilins are involved in the formation, organization, and maintenance of synapses, the specialized junctions where neurons communicate. There are three main types: LPHN1, LPHN2, and LPHN3, each with distinct yet related functions in the brain. These proteins bind to other molecules to guide synaptic development and function.
Role Beyond the Brain
While their functions in the nervous system are well-studied, latrophilins are not exclusively found in brain tissue. These proteins also play roles in cell adhesion and signaling in various other parts of the body.
Research indicates a connection between latrophilins and certain types of cancer. In some cancerous conditions, these proteins can influence processes related to tumor growth and spread. They may impact cancer cell migration, proliferation, and the formation of new blood vessels that supply tumors. This involvement suggests their potential as targets for future cancer research.
Latrophilins and Human Health
Dysfunction in latrophilin proteins can have implications for human health, as research shows their involvement in various conditions. A notable example is the link between genetic variations in the LPHN3 gene and an increased risk for Attention-Deficit/Hyperactivity Disorder (ADHD). These genetic differences can lead to an altered or faulty LPHN3 protein.
A modified latrophilin protein could disrupt the formation and function of synapses, particularly in brain regions associated with attention and impulse control. Such disruptions in synaptic architecture and signaling pathways are thought to contribute to the symptoms of ADHD. Understanding these molecular connections provides insights into the biological underpinnings of the disorder.