PHRs: bridging axon guidance, outgrowth and synapse development

Axon guidance, outgrowth, and synapse formation are interrelated developmental events during the maturation of the nervous system. Establishing proper synaptic connectivity requires precise axon navigation and a coordinated switch between axon outgrowth and synaptogenesis. The PHR (human Pam, mouse Phr1, zebrafish Esrom, DrosophilaHighwire, and C. elegansRPM-1) protein family regulates both axon and synapse development through their biochemical and functional interactions with multiple signaling pathways. Recent studies have begun to elucidate a common underlying mechanism for PHR functions: Consisting of motifs that affect intracellular signaling, selective protein degradation, and cytoskeleton organization, PHR proteins probably mediate the transition between axon outgrowth and synaptogenesis through integrating intracellular signaling and microtubule remodeling.