SRF Phosphorylation by Glycogen Synthase Kinase-3 Promotes Axon Growth in Hippocampal Neurons


Autoria(s): Li, Cong L; Sathyamurthy, Aruna; Oldenborg, Anna; Tank, Dharmesh; Ramanan, Narendrakumar
Data(s)

2014

Resumo

The growth of axons is an intricately regulated process involving intracellular signaling cascades and gene transcription. We had previously shown that the stimulus-dependent transcription factor, serum response factor (SRF), plays a critical role in regulating axon growth in the mammalian brain. However, the molecular mechanisms underlying SRF-dependent axon growth remains unknown. Here we report that SRF is phosphorylated and activated by GSK-3 to promote axon outgrowth in mouse hippocampal neurons. GSK-3 binds to and directly phosphorylates SRF on a highly conserved serine residue. This serine phosphorylation is necessary for SRF activity and for its interaction with MKL-family cofactors, MKL1 and MKL2, but not with TCF-family cofactor, ELK-1. Axonal growth deficits caused by GSK-3 inhibition could be rescued by expression of a constitutively active SRF. The SRF target gene and actin-binding protein, vinculin, is sufficient to overcome the axonal growth deficits of SRF-deficient and GSK-3-inhibited neurons. Furthermore, short hairpin RNA-mediated knockdown of vinculin also attenuated axonal growth. Thus, our findings reveal a novel phosphorylation and activation of SRF by GSK-3 that is critical for SRF-dependent axon growth in mammalian central neurons.

Formato

application/pdf

Identificador

http://eprints.iisc.ernet.in/48946/1/jou_neu_34-11_4027_2014.pdf

Li, Cong L and Sathyamurthy, Aruna and Oldenborg, Anna and Tank, Dharmesh and Ramanan, Narendrakumar (2014) SRF Phosphorylation by Glycogen Synthase Kinase-3 Promotes Axon Growth in Hippocampal Neurons. In: JOURNAL OF NEUROSCIENCE, 34 (11). pp. 4027-4042.

Publicador

SOC NEUROSCIENCE

Relação

http://dx.doi.org/10.1523/JNEUROSCI.4677-12.2014

http://eprints.iisc.ernet.in/48946/

Palavras-Chave #Centre for Neuroscience
Tipo

Journal Article

PeerReviewed