Synaptic adhesion-like molecules (SALMs)

Abstract

The synaptic adhesion-like molecules (SALMs) are a newly discovered family of cell adhesion molecules that have a variety of functions in neuronal development, including aspects of neurite outgrowth and synapse formation (Ko et al. Neuron 50:233-245, 2006, Morimura et al. Gene 380:72-83, 2006, Wang et al. J Neurosci 26:2174-2183, 2006, Seabold et al. J Biol Chem 283:8395-8405, 2008, Wang et al. Mol Cell Neurosci, 39:83-94, 2008). Also known as Lrfn (leucine-rich and fibronectin III domain-containing), five family members have been identified thus far: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. The SALMs have been shown to interact with NMDA receptors and the PSD-95 family of MAGUK proteins. Recent studies also indicate that the individual SALMs, while similar in structure, play distinct roles in heteromeric and homomeric protein interactions and neurite outgrowth (Seabold et al. J Biol Chem 283:8395-8405, 2008, Wang et al. Mol Cell Neurosci, 39:83-94, 2008). Neurite outgrowth and synapse formation are fundamental mechanisms in the development of the nervous system. While a considerable amount of information is known about both phenomena, the mechanism connecting the two is still enigmatic. SALMs join a growing mosaic of synaptic proteins that contribute to both neurite outgrowth and synapse formation during the course of development. Investigating SALMs and related proteins is essential for addressing fundamental questions of neuronal development.