Plasticity-related gene 5 (PRG5) induces filopodia and neurite growth and impedes lysophosphatidic acid- and nogo-A-mediated axonal retraction.
Members of the plasticity-related gene (PRG1-4) family are brain-specific integral membrane proteins and implicated in neuronal plasticity, such as filopodia formation and axon growth after brain lesion. Here we report on the cloning of a novel member of the PRG family, PRG5, with high homologies to PRG3. PRG5 is regulated during brain and spinal cord development and is exclusively allocated within the nervous system. When introduced in neurons, PRG5 is distributed in the plasma membrane and induces filopodia as well as axon elongation and growth. Conversely, siRNA mediated knockdown of PRG5 impedes axon growth and disturbs filopodia formation. Here we show that PRG5 induces filopodia growth independently of Cdc42. Moreover, axon collapse and RhoA activation induced by LPA and myelin-associated neurite inhibitor Nogo-A is attenuated in the presence of PRG5, although direct activation of the RhoA-Rho-PIP5K kinase pathway abolishes PRG5 -formed neurites. Thus, we describe here the identification of a novel member of the PRG family that induces filopodia and axon elongation in a Cdc42-independent manner. In addition, PRG5 impedes brain injury-associated growth inhibitory signals upstream of the RhoA-Rho kinase pathway.
Broggini
Thomas
T
Institute of Cell Biology and Neurobiology, Center of Anatomy, Charité-Universitätsmedizin Berlin, D-10117 Berlin, Germany.
Nitsch
Robert
R
Savaskan
Nic E
NE
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002478:Cells, Cultured; D008246:Lysophospholipids / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000502:physiology; D000070798:Nogo Proteins; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D008246:Lysophospholipids; D008565:Membrane Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; D034741:RNA, Small Interfering; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat; D054460:rho-Associated Kinases; C550842:plasticity-related gene 5 protein, mouse; D010744:Phosphoric Monoester Hydrolases; D020764:cdc42 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; C032881:lysophosphatidic acid