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

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.

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Abstract

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.

Item Type:	Journal Article
Publication:	JOURNAL OF NEUROSCIENCE
Publisher:	SOC NEUROSCIENCE
Additional Information:	copyright for this article belongs to SOC NEUROSCIENCE, 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
Keywords:	axon growth; filopodia; GSK-3; neurite outgrowth; serum response factor
Department/Centre:	Division of Biological Sciences > Centre for Neuroscience
Date Deposited:	18 Jun 2014 05:54
Last Modified:	18 Jun 2014 05:54
URI:	http://eprints.iisc.ac.in/id/eprint/48946

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