title: Bilateral crosstalk of rho- and extracellular-signal-regulated-kinase (ERK) pathways is confined to an unidirectional mode in spinal muscular atrophy (SMA).
abstract: Rho-kinase (ROCK) as well as extracellular signal regulated kinase (ERK) control actin cytoskeletal organization thereby regulating dynamic changes of cellular morphology. In neurons, motility processes such as axonal guidance and neurite outgrowth demand a fine regulation of upstream pathways. Here we demonstrate a bilateral ROCK-ERK information flow in neurons. This process is shifted towards an unidirectional crosstalk in a model of the neurodegenerative disease Spinal Muscular Atrophy (SMA), ultimately leading to neurite outgrowth dysregulations. As both pathways are of therapeutic relevance for SMA, our results argue for a combinatorial ROCK/ERK-targeting as a future treatment strategy.
authors: Institute of Neuroanatomy, Hannover Medical School, 30625 Hannover, Germany; Center for Systems Neuroscience (ZSN), 30559 Hannover, Germany.
authors: Niko
authors: N
authors: Hensel
authors: Institute of Neuroanatomy, Hannover Medical School, 30625 Hannover, Germany.
authors: Inga
authors: I
authors: Stockbrügger
authors: Institute of Neuroanatomy, Hannover Medical School, 30625 Hannover, Germany; Center for Systems Neuroscience (ZSN), 30559 Hannover, Germany.
authors: Sebastian
authors: S
authors: Rademacher
authors: Institute of Neuroanatomy, Hannover Medical School, 30625 Hannover, Germany.
authors: Natasha
authors: N
authors: Broughton
authors: Institute of Neuroanatomy, Hannover Medical School, 30625 Hannover, Germany.
authors: Hella
authors: H
authors: Brinkmann
authors: Institute of Neuroanatomy, Hannover Medical School, 30625 Hannover, Germany; Center for Systems Neuroscience (ZSN), 30559 Hannover, Germany.
authors: Claudia
authors: C
authors: Grothe
authors: Institute of Neuroanatomy, Hannover Medical School, 30625 Hannover, Germany; Center for Systems Neuroscience (ZSN), 30559 Hannover, Germany; Niedersachsen Research Network on Neuroinfection (N-RENNT), Germany. Electronic address: claus.peter@mh-hannover.de.
authors: Peter
authors: P
authors: Claus
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009134:Muscular Atrophy, Spinal / Q000473:pathology*; D016501:Neurites / Q000473:pathology*; D016716:PC12 Cells; D011720:Pyrazoles / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors; D055532:SMN Complex Proteins / Q000235:genetics*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; C505241:FR 180204; C115711:PD 173074; D011720:Pyrazoles; D011724:Pyridazines; D011725:Pyridines; D011743:Pyrimidines; D034741:RNA, Small Interfering; D017468:Receptors, Fibroblast Growth Factor; D055532:SMN Complex Proteins; C108830:Y 27632; D020794:Receptor Protein-Tyrosine Kinases; D054460:rho-Associated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: (ERK); (ROCK); (SMA); Neurite outgrowth; Nuclear protein; Rho-kinase; Spinal Muscular Atrophy; Survival of motoneuron protein; extracellular signal regulated kinase