AUTHOR=Ferrer-Ferrer Maura , Dityatev Alexander TITLE=Shaping Synapses by the Neural Extracellular Matrix JOURNAL=Frontiers in Neuroanatomy VOLUME=12 YEAR=2018 URL=https://www.frontiersin.org/journals/neuroanatomy/articles/10.3389/fnana.2018.00040 DOI=10.3389/fnana.2018.00040 ISSN=1662-5129 ABSTRACT=

Accumulating data support the importance of interactions between pre- and postsynaptic neuronal elements with astroglial processes and extracellular matrix (ECM) for formation and plasticity of chemical synapses, and thus validate the concept of a tetrapartite synapse. Here we outline the major mechanisms driving: (i) synaptogenesis by secreted extracellular scaffolding molecules, like thrombospondins (TSPs), neuronal pentraxins (NPs) and cerebellins, which respectively promote presynaptic, postsynaptic differentiation or both; (ii) maturation of synapses via reelin and integrin ligands-mediated signaling; and (iii) regulation of synaptic plasticity by ECM-dependent control of induction and consolidation of new synaptic configurations. Particularly, we focused on potential importance of activity-dependent concerted activation of multiple extracellular proteases, such as ADAMTS4/5/15, MMP9 and neurotrypsin, for permissive and instructive events in synaptic remodeling through localized degradation of perisynaptic ECM and generation of proteolytic fragments as inducers of synaptic plasticity.