Neurexins:: three genes and 1001 products

The human brain has approximately 10(12) neurons, three orders of magnitude more than there are basepairs in the human genome. Each neuron is connected to other neurons by thousands of synapses, creating a dense network of communicating neurons. Cell-recognition events between neurons at, and outside of synapses, are likely to guide the development and maintenance of the complex network formed by neurons. However, little is known about which proteins are important for neuronal cell recognition. Neurexins, a family of polymorphic cell-surface proteins, might mediate some of these cell recognition events. Thousands of neurexin isoforms are generated from three genes by usage of alternative promoters and alternative splicing. These isoforms are displayed on the neuronal cell surface, with different classes of neurons expressing distinct combinations of isoforms. Neurexins probably have a multitude of ligands, some of which interact only with subsets of neurexin isoforms. This review describes the properties of the neurexin protein family and their potential roles in neuronal cell adhesion and intercellular signaling.