Explore chapters and articles related to this topic
Lipid Raft Alteration and Functional Impairment in Aged Neuronal Membranes
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
Julie Colin, Lynn Gregory-Pauron, Frances T. Yen, Thierry Oster, Catherine Malaplate-Armand
Recruitment of receptors into rafts can be necessary for activation of specific signaling pathways, as in the case of the activation of the TrkA receptor by nerve growth factor (NGF), or TrkB receptor by brain-derived neurotrophic factor (BDNF) [147–149]. Other examples point toward ligand-induced relocation of membrane receptors in various cell types. Indeed, the epidermal growth factor (EGF) receptor locates outside of rafts when activated by its ligand, as shown in b82 and NR6 mouse fibroblasts [150], whereas the insulin growth factor (IGF) receptor is recruited into rafts upon treatment of human hepatoma HuH7 cells by insulin [151]. Moreover, the NGF-activated (phosphorylated) and palmitoylated TrkA and p75NTR receptors are clustered in the caveolae-like domains of the plasma membrane in mouse 3T3 fibroblasts and in PC12 cells treated with their ligand, but not after caveolae disruption by filipin [152]. Recently, SH-SY5Y cells were used as dopaminergic neurons to demonstrate that the neuroprotective effect of glial cell line-derived neurotrophic factor (GDNF) is influenced by the relocation of NCAM-140 into rafts, which can be suppressed by palmitoylation inhibition [153].
The Occurrence of Valvular Atrial Fibrillation: Involvement of NGF/TrKA Signaling Pathway
Published in Journal of Investigative Surgery, 2021
Qianli Wang, Yong Zhao, Xin Dong, Cong Li, Lin Zhou, Chengwei Zou, Xiaodong Li, Nannan Zhou, Junni Liu, Yuanyuan Sun, Jianchun Wang
TrkA is a specific trk receptor that binds to NGF and is crucial for maintaining sympathetic neuron health and stimulating axon regeneration. Previous studies have demonstrated that NGF/TrkA signaling play an important role in enhancing normal cardiac calcium cycling and normal cardiovascular system function [21,22]. After the association between NGF and the TrkA receptor was demonstrated, it was revealed that this triggers TrkA receptor autophosphorylation. Therefore, the protein level of TrkA phosphorylation of Trk was investigated in this study. The TrkA protein level was decreased in AF patients. The results from this study also indicated that activation of the downstream Akt pathway was inhibited, which was detected by the phosphorylation of its mediators Akt. In addition, proper TrkA transport and sorting mediates the function of NGF. However, the concentration of TrKA did not increase with the increasing of NGF. Previous studies illustrated that stimulated cells with NGF and measured TrkA at different times, TrKA concentration decreased with time due to TrkA degradation [23,24]. This may explain the decreasion of TrkA concentration. Thus, as NGF/TrkA signaling was necessary for the function of neurotrophins in both neurons and heart, it was speculated that neurotrophic signaling may be a key factor of the AF patients.
NGF/TrKA Signaling Pathway and Atrial Fibrillation: Is There a Link?
Published in Journal of Investigative Surgery, 2021
Nerve growth factor (NGF), the first neurotrophin (NT) to be discovered, is a homodimer composed of two non-covalently bound chains that exerts its actions through two structurally unrelated transmembrane receptors—the TrkA receptor tyrosine-kinase, which is specific for NGF, and the p75NTR receptor, a tumor necrosis factor receptor family member that is shared among all NTs [5]. NGF is known to be the main contributor to cardiac sympathetic innervation density. It has been previously shown that ET-1 (Endothelin-1) signaling pathway contributes to an increase in NGF expression, while Cn-NFAT (Calcineurin-Nuclear Factor of Activated T Cells) signaling pathway significantly depresses NGF expression. However, the molecular mechanisms involved in atrial fibrillation, still remain unclear [6].
Potential of Müller Glia for Retina Neuroprotection
Published in Current Eye Research, 2020
Karen Eastlake, Joshua Luis, G Astrid Limb
NGF is a prototypic neurotrophin, with properties and functions that define the neurotrophic family of growth factor polypeptides. It signals with high affinity through the TrkA receptor and plays a pivotal role during the development, maintenance, and regeneration of sensory neurons in the CNS.45 It is highly expressed in the human eye during development and its mature form selectively binds to TrkA, promoting neural cell survival within the retina, in particular of retinal ganglion cells (RGCs).46 In addition to its neurotrophic functions on retinal neurons, NGF has been shown to be a potent antioxidant, as demonstrated by its effect in preventing oxidant-induced lipid peroxide production by Müller glia in response to H2O2 -induced oxidative stress.47