Target-Derived Matricryptins Organize Cerebellar Synapse Formation through α3β1 Integrins

SummaryTrans-synaptic organizing cues must be passed between synaptic partners for synapses to properly form. Much of our understanding of this process stems from studies at the neuromuscular junction, where target-derived growth factors, extracellular matrix (ECM) molecules, and matricryptins (proteolytically released fragments of ECM molecules) are all essential for the formation and maintenance of motor nerve terminals. While growth factors and ECM molecules also contribute to the formation of brain synapses, it remains unclear whether synaptic roles exist for matricryptins in the mammalian brain. We report that collagen XVIII and its matricryptin endostatin are generated by cerebellar Purkinje cells and are necessary for the organization of climbing fiber terminals in these neurons. Moreover, endostatin is sufficient to induce climbing fiber terminal formation in vitro by binding and signaling through α3β1 integrins. Taken together, these studies reveal roles for both matricryptins and integrins in the organization of brain synapses.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Endostatin, a collagen XVIII-derived matricryptin, is generated by Purkinje cells ► Proper organization of climbing fiber terminals requires collagen XVIII/endostatin ► Application of endostatin induces climbing fiber terminal formation in vitro ► Endostatin binds and signals through α3β1 integrins