title: The SALM/Lrfn family of leucine-rich repeat-containing cell adhesion molecules.
abstract: Synaptic adhesion molecules play important roles in various stages of neuronal development, including neurite outgrowth and synapse formation. The SALM (synaptic adhesion-like molecule) family of adhesion molecules, also known as Lrfn, belongs to the superfamily of leucine-rich repeat (LRR)-containing adhesion molecules. Proteins of the SALM family, which includes five known members (SALMs 1-5), have been implicated in the regulation of neurite outgrowth and branching, and synapse formation and maturation. Despite sharing a similar domain structure, individual SALM family proteins appear to have distinct functions. SALMs 1-3 contain a C-terminal PDZ-binding motif, which interacts with PSD-95, an abundant postsynaptic scaffolding protein, whereas SALM4 and SALM5 lack PDZ binding. SALM1 directly interacts with NMDA receptors but not with AMPA receptors, whereas SALM2 associates with both NMDA and AMPA receptors. SALMs 1-3 form homo- and heteromeric complexes with each other in a cis manner, whereas SALM4 and SALM5 do not, but instead participate in homophilic, trans-cellular adhesion. SALM3 and SALM5, but not other SALMs, possess synaptogenic activity, inducing presynaptic differentiation in contacting axons. All SALMs promote neurite outgrowth, while SALM4 uniquely increases the number of primary processes extending from the cell body. In addition to these functional diversities, the fifth member of the SALM family, SALM5/Lrfn5, has recently been implicated in severe progressive autism and familial schizophrenia, pointing to the clinical importance of SALMs.
authors: National Creative Research Initiative Center for Synaptogenesis, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
authors: Jungyong
authors: J
authors: Nam
authors: Won
authors: W
authors: Mah
authors: Eunjoon
authors: E
authors: Kim
mesh_terms: D000595:Amino Acid Sequence; D001321:Autistic Disorder / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry* / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D000090263:Leucine-Rich Repeat Proteins; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D018091:Receptors, AMPA / Q000737:chemistry / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics; D013569:Synapses / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; C561460:LRFN4 protein, human; D000090263:Leucine-Rich Repeat Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; C476198:RTN3 protein, human; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C106354:flotillins; C555156:synaptic adhesion-like molecule 4, rat