Abstract
Lipid rafts, cholesterol and lipid rich microdomains, are believed to play important roles as platforms for the partitioning of transmembrane and synaptic proteins involved in synaptic signaling, plasticity, and maintenance. There is increasing evidence of a physical interaction between post-synaptic densities and post-synaptic lipid rafts. Localization of proteins within lipid rafts is highly regulated, and therefore lipid rafts may function as traffic lights modulating and fine-tuning neuronal signaling. The tyrosine kinase neurotrophin receptors (Trk) and the low-affinity p75 neurotrophin receptor (p75NTR) are enriched in neuronal lipid rafts together with the intermediates of downstream signaling pathways, suggesting a possible role of rafts in neurotrophin signaling. Moreover, neurotrophins and their receptors are involved in the regulation of cholesterol metabolism. Cholesterol is an important component of lipid rafts and its depletion leads to gradual loss of synapses, underscoring the importance of lipid rafts for proper neuronal function. Here, we review and discuss the idea that translocation of neurotrophin receptors in synaptic rafts may account for the selectivity of their transduced signals.
Highlights
One can hypothesize that brain derived neurotrophic factor (BDNF)-stimulated TrkB signaling could potentially coordinate the delivery of key molecules at post-synaptic lipid rafts to promote synaptic plasticity (Figure 1)
CONCLUDING REMARKS In summary, the literature reviewed here is alluding to the idea that neurotrophin signaling may occur by recruitment of neurotrophin receptors at specific sites on the cell surface and/or in internal compartments that might be distinct from signaling endosomes
This recruitment, if occurring at synaptic rafts, might elicit activation of distinct signaling pathways involved in synaptic plasticity
Summary
Edited by: Nancy Ip, The Hong Kong University of Science and Technology, Hong Kong. Reviewed by: Philippe Marin, University of Montpellier, France Fabrice Ango, University of Montpellier, France. Cholesterol and lipid rich microdomains, are believed to play important roles as platforms for the partitioning of transmembrane and synaptic proteins involved in synaptic signaling, plasticity, and maintenance. Localization of proteins within lipid rafts is highly regulated, and lipid rafts may function as traffic lights modulating and fine-tuning neuronal signaling. The tyrosine kinase neurotrophin receptors (Trk) and the low-affinity p75 neurotrophin receptor (p75NTR) are enriched in neuronal lipid rafts together with the intermediates of downstream signaling pathways, suggesting a possible role of rafts in neurotrophin signaling. Neurotrophins and their receptors are involved in the regulation of cholesterol metabolism.
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