Developing dendritic spines need to hold on tight to the extracellular matrix as they seek out partnering neurons. Once they find partners, however, the spine tips must sever their matrix ties to reshape into post-synaptic receiving stations, according to Tian et al. (page 687).

Dendritic spine growth and maturation coincides with the expression of a neuron-specific transmembrane adhesion molecule called ICAM-5. Spines in mice lacking ICAM-5 grow more slowly but mature more quickly, suggesting that the adhesion molecule is needed for spines to find partners but inhibits their subsequent maturation.

Tian et al. now show that spine maturation is possible in neurons because much of ICAM-5 is cleaved into a nonadhesive form during synaptogenesis. This cleavage was promoted by neuron stimulation through receptors for the NMDA and AMPA neurotransmitters.

Receptor activation caused ICAM-5 to be released from the actin cytoskeleton, which in turn promoted its cleavage. Release from the actin network might make it susceptible to destructive enzymes such as the MMP2 and MMP9 matrix metalloproteases, which were needed for ICAM-5 cleavage.