The PHR proteins: intracellular signaling hubs in neuronal development and axon degeneration

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• 作者：Brock Grill ; Rodney K. Murphey ; Melissa A. Borgen
• 关键词：Synapse formation ; Axon termination ; Axon guidance ; Axon degeneration ; Phr1 ; Pam ; MYCBP2 ; Highwire ; RPM ; 1 ; PHR protein
• 刊名：Neural Development
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：11
• 期：1
• 全文大小：1,749 KB
• 刊物主题：Neurosciences; Developmental Biology;
• 出版者：BioMed Central
• ISSN：1749-8104

文摘

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.