Protocadherin-17 Mediates Collective Axon Extension by Recruiting Actin Regulator Complexes to Interaxonal Contacts

•Amygdala axons fail to grow normally in the absence of protocadherin-17 (Pcdh17)•Amygdala axons expressing ectopic Pcdh17 are misrouted during extension•Pcdh17 recruits the WAVE complex, Lamellipodin, and Ena/VASP to axon-axon contacts•The Pcdh17-mediated recruitment of actin regulators enhances cell motility

SummaryIn the process of neuronal wiring, axons derived from the same functional group typically extend together, resulting in fascicle formation. How these axons communicate with one another remains largely unknown. Here, we show that protocadherin-17 (Pcdh17) supports this group extension by recruiting actin polymerization regulators to interaxonal contact sites. Pcdh17 is expressed by a subset of amygdala neurons, and it accumulates at axon-axon boundaries because of homophilic binding. Pcdh17 knockout in mice suppressed the extension of these axons. Ectopically expressed Pcdh17 altered the pattern of axon extension. In in vitro cultures, wild-type growth cones normally migrate along other axons, whereas Pcdh17 null growth cones do not. Pcdh17 recruits the WAVE complex, Lamellipodin, and Ena/VASP to cell-cell contacts, converting these sites into motile structures. We propose that, through these mechanisms, Pcdh17 maintains the migration of growth cones that are in contact with other axons, thereby supporting their collective extension.

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