Structural highlights
Function
[LRFN1_MOUSE] Promotes neurite outgrowth in hippocampal neurons. Involved in the regulation and maintenance of excitatory synapses. Induces the clustering of excitatory postsynaptic proteins, including DLG4, DLGAP1, GRIA1 and GRIN1.[1] [2]
Publication Abstract from PubMed
Synapse formation is triggered by trans-synaptic interactions of cell adhesion molecules, termed synaptic organizers. Three members of type-II receptor protein tyrosine phosphatases (classified as type-IIa RPTPs; PTPdelta, PTPsigma and LAR) are known as presynaptic organizers. Synaptic adhesion-like molecules (SALMs) have recently emerged as a family of postsynaptic organizers. Although all five SALM isoforms can bind to the type-IIa RPTPs, only SALM3 and SALM5 reportedly have synaptogenic activities depending on their binding. Here, we report the crystal structures of apo-SALM5, and PTPdelta-SALM2 and PTPdelta-SALM5 complexes. The leucine-rich repeat (LRR) domains of SALMs interact with the second immunoglobulin-like (Ig) domain of PTPdelta, whereas the Ig domains of SALMs interact with both the second and third Ig domains of PTPdelta. Unexpectedly, the structures exhibit the LRR-mediated 2:2 complex. Our synaptogenic co-culture assay using site-directed SALM5 mutants demonstrates that presynaptic differentiation induced by PTPdelta-SALM5 requires the dimeric property of SALM5.
Structural basis of trans-synaptic interactions between PTPdelta and SALMs for inducing synapse formation.,Goto-Ito S, Yamagata A, Sato Y, Uemura T, Shiroshima T, Maeda A, Imai A, Mori H, Yoshida T, Fukai S Nat Commun. 2018 Jan 18;9(1):269. doi: 10.1038/s41467-017-02417-z. PMID:29348429[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Morimura N, Inoue T, Katayama K, Aruga J. Comparative analysis of structure, expression and PSD95-binding capacity of Lrfn, a novel family of neuronal transmembrane proteins. Gene. 2006 Oct 1;380(2):72-83. Epub 2006 Jun 3. PMID:16828986 doi:http://dx.doi.org/S0378-1119(06)00340-4
- ↑ Wang PY, Seabold GK, Wenthold RJ. Synaptic adhesion-like molecules (SALMs) promote neurite outgrowth. Mol Cell Neurosci. 2008 Sep;39(1):83-94. doi: 10.1016/j.mcn.2008.05.019. Epub, 2008 Jun 7. PMID:18585462 doi:http://dx.doi.org/10.1016/j.mcn.2008.05.019
- ↑ Goto-Ito S, Yamagata A, Sato Y, Uemura T, Shiroshima T, Maeda A, Imai A, Mori H, Yoshida T, Fukai S. Structural basis of trans-synaptic interactions between PTPdelta and SALMs for inducing synapse formation. Nat Commun. 2018 Jan 18;9(1):269. doi: 10.1038/s41467-017-02417-z. PMID:29348429 doi:http://dx.doi.org/10.1038/s41467-017-02417-z
