PT  - JOURNAL ARTICLE
AU  - Sina Stern
AU  - Stephanie Haverkamp
AU  - Daniela Sinske
AU  - Andrea Tedeschi
AU  - Ulrike Naumann
AU  - Simone Di Giovanni
AU  - Stefan Kochanek
AU  - Alfred Nordheim
AU  - Bernd Knöll
TI  - The Transcription Factor Serum Response Factor Stimulates Axon Regeneration through Cytoplasmic Localization and Cofilin Interaction
AID  - 10.1523/JNEUROSCI.3029-13.2013
DP  - 2013 Nov 27
TA  - The Journal of Neuroscience
PG  - 18836--18848
VI  - 33
IP  - 48
4099  - http://www.jneurosci.org/content/33/48/18836.short
4100  - http://www.jneurosci.org/content/33/48/18836.full
SO  - J. Neurosci.2013 Nov 27; 33
AB  - Axonal injury generates growth inert retraction bulbs with dynamic cytoskeletal properties that are severely compromised. Conversion of “frozen” retraction bulbs into actively progressing growth cones is a major aim in axon regeneration. Here we report that murine serum response factor (SRF), a gene regulator linked to the actin cytoskeleton, modulates growth cone actin dynamics during axon regeneration. In regeneration-competent facial motoneurons, Srf deletion inhibited axonal regeneration. In wild-type mice after nerve injury, SRF translocated from the nucleus to the cytoplasm, suggesting a cytoplasmic SRF function in axonal regeneration. Indeed, adenoviral overexpression of cytoplasmic SRF (SRF-ΔNLS-GFP) stimulated axonal sprouting and facial nerve regeneration in vivo. In primary central and peripheral neurons, SRF-ΔNLS-GFP stimulated neurite outgrowth, branch formation, and growth cone morphology. Furthermore, we uncovered a link between SRF and the actin-severing factor cofilin during axonal regeneration in vivo. Facial nerve axotomy increased the total cofilin abundance and also nuclear localization of phosphorylated cofilin in a subpopulation of lesioned motoneurons. This cytoplasmic-to-nucleus translocation of P-cofilin upon axotomy was reduced in motoneurons expressing SRF-ΔNLS-GFP. Finally, we demonstrate that cytoplasmic SRF and cofilin formed a reciprocal regulatory unit. Overexpression of cytoplasmic SRF reduced cofilin phosphorylation and vice versa: overexpression of cofilin inhibited SRF phosphorylation. Therefore, a regulatory loop consisting of SRF and cofilin might take part in reactivating actin dynamics in growth-inert retraction bulbs and facilitating axon regeneration.