title: Homeoprotein signaling in development, health, and disease: a shaking of dogmas offers challenges and promises from bench to bed.
abstract: Homeoproteins constitute a major class of transcription factors active throughout development and in adulthood. Their membrane transduction properties were discovered over 20 years ago, opening an original field of research in the domain of vector peptides and signal transduction. In early development, homeoprotein transfer participates in tissue patterning, cell/axon guidance, and migration. In the axon guidance model, homeoproteins exert their non-cell autonomous activity through the regulation of translation, in particular, that of nuclear-transcribed mitochondrial mRNAs. An important aspect of these studies on patterning and migration is that homeoproteins sensitize the cells to the action of other growth factors, thus cooperating with established signaling pathways. The role of homeoprotein signaling at later developmental stages is also of interest. In particular, the transfer of homeoprotein Otx2 into parvalbumin-expressing inhibitory neurons (PV-cells) in the visual cortex regulates cortical plasticity. The molecular deciphering of the interaction of Otx2 with binding sites at the surface of PV-cells has allowed the development of a specific Otx2 antagonist that reopens plasticity in the adult cortex and cures mice from experimental amblyopia, a neurodevelopmental disease. Finally, the use of homeoproteins as therapeutic proteins in mouse models of glaucoma and Parkinson disease is reviewed. In the latter case, engrailed homeoproteins protect mesencephalic dopaminergic neurons by increasing the local translation of complex I mitochondrial mRNAs. In conclusion, this review synthesizes 20 years of work on the fundamental and potentially translational aspects of homeoprotein signaling.
authors.affiliation: Development and Neuropharmacology Group, College de France, Centre for Interdisciplinary Research in Biology, CNRS UMR 7241/INSERM U1050, Labex Memolife, PSL Research University, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Spatazza
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Di Lullo
authors.forename: Alain
authors.initials: A
authors.lastname: Joliot
authors.forename: Edmond
authors.initials: E
authors.lastname: Dupont
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Moya
authors.forename: Alain
authors.initials: A
authors.lastname: Prochiantz
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D002465:Cell Movement; D057846:Cell-Penetrating Peptides; D018398:Homeodomain Proteins / Q000502:physiology*; D009473:Neuronal Plasticity; D015398:Signal Transduction; D014793:Visual Cortex / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D018398:Homeodomain Proteins; C414409:penetratin