"In the brain, reticulon 3 (RTN3) tightly associates with SALM2 and SALM3 to form a complex, and interacts relatively weakly with SALM1 and SALM4."

"SALM3 and SALM5, but not other SALMs, induce presynaptic differentiation in contacting axons (Mah et al. 2010)."

"SALM1, SALM2, and SALM3 form homo- and heteromeric complexes in a cis manner."

"SALM1 can directly interact with the extracellular domain of the NR1 subunit of NMDA receptor or indirectly by binding to PSD-95, which may recruit NMDA receptor via the NR2 subunits of NMDA receptors"

"The family members, SALM1-SALM4, have a single transmembrane (TM) domain and contain extracellular leucine-rich repeats, an Ig C2 type domain, a fibronectin type III domain, and an intracellular postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1 (PDZ) binding domain, which is present on all members except SALM4."

"SALM1 interacts with PSD-95, synapse-associated protein 102 (SAP102), and SAP97 based on coimmunoprecipitation of detergent-solubilized brain. Distribution studies show that SALM1 is present in synaptic membrane and postsynaptic density fractions but is also distributed in axons and dendrites."

"Overexpression of SALM1 in 14 DIV neurons recruits NMDA receptors (NR) and PSD-95 to dendritic puncta."

"Lrfn1-5 commonly encode glycoproteins spanning the plasma membrane, with their N-terminus located on the extracellular side."

"In the course of development, expression of Lrfn1, Lrfn3, and Lrfn4 started from immature neural cells, whereas that of Lrfn2 and Lrfn5 was limited to mature ones. Lrfn1-5 commonly encode glycoproteins spanning the plasma membrane, with their N-terminus located on the extracellular side. C-termini of Lrfn1, Lrfn2 and Lrfn4 were bound by PDZ domains of postsynaptic protein PSD95, re-distributing PSD95 to cell periphery where the Lrfn proteins were detected."

"In brain, we found that SALMs 1-3 strongly co-immunoprecipitated with each other, whereas SALMs 4 and 5 did not, suggesting that SALMs 4 and 5 mainly form homomeric complexes."

"Both SALMs 4 and 5 formed homophilic, but not heterophilic associations, whereas no trans associations were formed by the other SALMs."

"Over-expression of each SALM resulted in enhanced neurite outgrowth, but with different phenotypes. Neurite outgrowth could be reduced by applying antibodies targeting the extracellular leucine rich regions of SALMs and with RNAi. Through over-expression of deletion constructs, we found that the C-terminal PDZ binding domains of SALMs 1-3 are required for most aspects of neurite outgrowth."

"To identify proteins that interact with extracellular domains of SALMs, we carried out yeast two-hybrid screening using the extracellular domain of SALM1 as bait. A clone encoding full-length reticulon 3A1 was isolated. This interaction was shown to occur through the LRR domain, which is found on all SALMs."

"A 19-kDa band, identified as reticulon 3C, bound to all four SALMs, whereas a 90-kDa band, which did not comigrate with any known reticulon 3 variant, bound to SALMs 2 and 3."

"We found that expression of the SALM family proteins SALM3 and SALM5 in nonneural and neural cells induces both excitatory and inhibitory presynaptic differentiation in contacting axons."

"Lrfn2 expression increased in the postnatal cerebral cortex and hippocampus, (Fig. 1b), and Lrfn2 was the only Lrfn family member that prominently increased in postnatal hippocampus."

"The synapses are structurally and functionally immature with spindle shaped spines, smaller postsynaptic densities, reduced AMPA/NMDA ratio, and enhanced LTP."

"In vitro experiments reveal that synaptic surface expression of AMPAR depends on the direct interaction between Lrfn2 and PSD-95."

"Here, we found that mice lacking SALM1/LRFN2 (Lrfn2-/- mice) show a normal density of excitatory synapses but altered excitatory synaptic function, including enhanced NMDAR-dependent synaptic transmission but suppressed NMDAR-dependent synaptic plasticity in the hippocampal CA1 region. Unexpectedly, SALM1 expression was detected in both glutamatergic and GABAergic neurons and Lrfn2-/- CA1 pyramidal neurons showed decreases in the density of inhibitory synapses and the frequency of spontaneous inhibitory synaptic transmission."

"We show that SALM1 is present at pre‐ and postsynaptic membranes of mouse hippocampal neurons and that depletion of pre‐ or postsynaptic SALM1 impaired Neuroligin1‐ and Neurexin1β‐mediated excitatory synapse formation and reduced synaptic vesicle clustering, synaptic transmission, and synaptic vesicle release."

"Together, our data suggest that SALM1 organizes synapse development by promoting F‐actin/PIP2‐dependent cis‐oligomerization of Neurexin at the presynapse."

"Together, these data identify SALM1 as a novel binding partner of the CASK/Mint1/Lin7b presynaptic organizer complex, interacting directly with CASK, via its PDZ binding domain."

"This established that the isolated recombinant PDZ domain of SNX27 directly bound to a synthetic peptide corresponding to the LRFN2 PDZ binding motif, S-S-E-W-V-M-E−3-S-T-V−0 with a high micromolar affinity (Kd = 1.6 µM) (Figure 2D)."

"Furthermore, LRFN2 associates with AMPA receptors and knockdown of LRFN2 results in decreased surface AMPA receptor expression, reduced synaptic activity, and attenuated hippocampal long-term potentiation."

"LRFN2 is selectively expressed at cone terminals and colocalizes with PNA, and other DBC signalplex members."

"In the absence of LRFN2 the cone-mediated photopic electroretinogram b-wave amplitude is reduced at the brightest flash intensities. These data demonstrate that LRFN2 absence compromises normal synaptic transmission between cones and cone DBCs."