title: Rapid electrical and delayed molecular signals regulate the serum response element after nerve injury: convergence of injury and learning signals.
abstract: Axotomy elicits changes in gene expression, but little is known about how information from the site of injury is communicated to the cell nucleus. We crushed nerves in Aplysia californica and the sciatic nerve in the mouse and found short- and long-term activation of an Elk1-SRF transcription complex that binds to the serum response element (SRE). The enhanced short-term binding appeared rapidly and was attributed to the injury-induced activation of an Elk1 kinase that phosphorylates Elk1 at ser383. This kinase is the previously described Aplysia (ap) ERK2 homologue, apMAPK. Nerve crush evoked action potentials that propagated along the axon to the cell soma. Exposing axons to medium containing high K(+), which evoked a similar burst of spikes, or bathing the ganglia in 20 microM serotonin (5HT) for 20 min, activated the apMAPK and enhanced SRE binding. Since 5HT is released in response to electrical activity, our data indicate that the short-term process is initiated by an injury-induced electrical discharge that causes the release of 5HT which activates apMAPK. 5HT is also released in response to noxious stimuli for aversive learning. Hence, apMAPK is a point of convergence for injury signals and learning signals. The delay before the onset of the long-term SRE binding was reduced when the crush was closer to the ganglion and was attributed to an Elk1 kinase that is activated by injury in the axon and retrogradely transported to the cell body. Although this Elk1 kinase phosphorylates mammalian rElk1 at ser383, it is distinct from apMAPK.
authors.affiliation: Department of Anatomy and Cell Biology, 1201 Black Building, Columbia University, West 168th Street, New York, New York 10032, USA.
authors.forename: Hana
authors.initials: H
authors.lastname: Lin
authors.forename: Jianxin
authors.initials: J
authors.lastname: Bao
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Sung
authors.forename: Edgar T
authors.initials: ET
authors.lastname: Walters
authors.forename: Richard T
authors.initials: RT
authors.lastname: Ambron
authors.forename: Ju-Sung
authors.initials: JS
authors.lastname: Ying
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001048:Aplysia; D015153:Blotting, Western; D005786:Gene Expression Regulation; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D008954:Models, Biological; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation; D011233:Precipitin Tests; D036143:Receptor, EphA8 / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D027602:Serum Response Element / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D012701:Serotonin; D036143:Receptor, EphA8; D019950:Mitogen-Activated Protein Kinase 1