title: The PHR proteins: intracellular signaling hubs in neuronal development and axon degeneration.
abstract: During development, a coordinated and integrated series of events must be accomplished in order to generate functional neural circuits. Axons must navigate toward target cells, build synaptic connections, and terminate outgrowth. The PHR proteins (consisting of mammalian Phr1/MYCBP2, Drosophila Highwire and C. elegans RPM-1) function in each of these events in development. Here, we review PHR function across species, as well as the myriad of signaling pathways PHR proteins regulate. These findings collectively suggest that the PHR proteins are intracellular signaling hubs, a concept we explore in depth. Consistent with prominent developmental functions, genetic links have begun to emerge between PHR signaling networks and neurodevelopmental disorders, such as autism, schizophrenia and intellectual disability. Finally, we discuss the recent and important finding that PHR proteins regulate axon degeneration, which has further heightened interest in this fascinating group of molecules.
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, FL, 33458, USA. bgrill@scripps.edu.
authors.forename: Brock
authors.initials: B
authors.lastname: Grill
authors.affiliation: Department of Biological Sciences, Florida Atlantic University, Jupiter, FL, 33458, USA.
authors.forename: Rodney K
authors.initials: RK
authors.lastname: Murphey
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Scripps Florida, Jupiter, FL, 33458, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Borgen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D065886:Neurodevelopmental Disorders / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013045:Species Specificity; D013569:Synapses / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D020662:Guanine Nucleotide Exchange Factors; C409633:HIW protein, Drosophila; D009419:Nerve Tissue Proteins; C409634:RPM-1 protein, C elegans; C114022:MYCBP2 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Axon degeneration; Axon guidance; Axon termination; Highwire; MYCBP2; PHR protein; Pam; Phr1; RPM-1; Synapse formation