Making connections: cholinesterase-domain proteins in the CNS

Recent studies have highlighted novel functions of a group of cell adhesion molecules during nervous system development. Members of this protein family are characterized by an extracellular domain with sequence homology to cholinesterases and include the neuroligins, synaptic cell adhesion molecules recently implicated in autism, and neurotactin, a cell surface receptor involved in axonal pathfinding. Although these proteins have a structural organization similar to the enzyme acetylcholinesterase, the cholinesterase domain lacks enzymatic activity and functions as a protein-protein interaction motif. This protein family provides a striking example of how the function of a catalytically active domain has evolved to mediate receptor-ligand interactions that regulate morphogenetic processes during development of the nervous system.