Artemin activates axonal growth via SFK and ERK‐dependent signalling pathways in mature dorsal root ganglia neurons

Abstract

Artemin, one of the glial cell line-derived neurotrophic factor (GDNF) family, enhances the generation and survival of early sympathetic neurons and superior cervical ganglion (SCG) neurons. Src-family kinases (SFK) are involved in the growth and differentiation of cells, which are composed of unique Src homology 2 (SH2), Src homology 3 (SH3) and kinase domains. Various extra-cellular molecules containing growth factors and G-protein coupled receptors stimulate SFK. In this report, artemin is shown to have a significant effect on the neurite growth of dorsal root ganglia (DRG) neurons. Also, artemin triggers Src-family kinase activation and the phosphorylation of extra-cellular signal-regulated kinases (ERK) mitogen-activated protein kinase (MAPK). Artemin also regulated actin polymerization. There are several indications that another SH3-containing protein, Hck, and an SH3-containing adaptor protein, Nck1, play an important role in the organization of the actin cytoskeleton by cellular signalling. These findings suggest that the exploration of binding partners for the SH3 domain could provide an insight into regulation between the microtubule and actin networks. The binding partners for the SH3 domains of Nck, Src and Hck that we identified were Smc chromosome segregation ATPases, FOG Zn-finger protein and the FYVE zinc-binding domain, respectively.

Inflammation-induced shift in spinal GABAAsignaling is associated with a tyrosine kinase-dependent increase in GABAAcurrent density in nociceptive afferents

“…src phosphorylates ␤-and ␥ 2 -subunits of the GABA A receptor, resulting in an increase of GABA current (Brandon et al 2001;Moss et al 1995;Wan et al 1997), and the src kinase-selective inhibitor PP2 resulted in a significant reduction in the inflammation-induced increase in GABA current in cutaneous neurons. Because the concentration of PP2 employed should have been sufficient for complete block of src (Tong and Gibb 2008), the observation that the influence of PP2 was less than that of genistein raises the possibility that other tyrosine kinases such as fyn and hck (Jeong et al 2008;Jurd et al 2010) contributed to the inflammation-induced increase in GABA current.…”

Antidepressant-like effect of artemin in mice: a mechanism for acetyl-l-carnitine activity on depression

“…During embryonic development, ARTN enhances sympathetic neuroblast proliferation, survival of sympathetic neurons at distinct developmental stages, and neurite outgrowth from postnatal and adult sympathetic neurons (Andres et al 2001;Warnecke et al 2010). It also acts as a trophic factor and enhances survival of sensory and sympathetic peripheral neurons (Baloh et al 1998;Jeong et al 2008). ARTN is expressed in structures of the basal ganglia (subthalamic nucleus, putamen, and substantia nigra), thalamus, and many peripheral adult human tissues (Baloh et al 1998), and it is a potent neurotrophic factor that may play an important role in the structural development and plasticity of ventral mesencephalic dopaminergic neurons (Zihlmann et al 2005).…”

c-Jun Gene-Modified Schwann Cells: Upregulating Multiple Neurotrophic Factors and Promoting Neurite Outgrowth

“…19,20 Artn exerts multiple effects on sensory neuron generation, survival, regeneration, and functional recovery. [38][39][40][41] LIF has also been shown to play a positive role in nerve regeneration. 42 These findings highlight the importance of combining a cellular substrate with NFs to promote nerve regeneration.…”