Structural basis of trans-synaptic interactions between PTP? and SALMs for inducing synapse formation.

ABSTRACT: 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; PTP?, PTP? 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 PTP?-SALM2 and PTP?-SALM5 complexes. The leucine-rich repeat (LRR) domains of SALMs interact with the second immunoglobulin-like (Ig) domain of PTP?, whereas the Ig domains of SALMs interact with both the second and third Ig domains of PTP?. 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 PTP?-SALM5 requires the dimeric property of SALM5.

SUBMITTER: Goto-Ito S 

PROVIDER: S-EPMC5773591 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature