Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8480694 | Seminars in Cell & Developmental Biology | 2014 | 7 Pages |
Abstract
Neurotrophins play a critical role in neuronal development and survival, as well as maintenance of the adult nervous system. Neurotrophins can mediate their effects by signalling locally at the nerve terminal, or signalling retrogradely from the axonal terminal to the cell soma to regulate gene expression. Given that the axon terminals of many nerve cells can be up to a metre away from their soma, neurons have evolved specialized long-range signalling platforms that depend on a highly regulated network of intracellular membrane compartments termed “signalling endosomes”. Endosomal trafficking of activated receptors controls not only the axonal retrograde signals but also local receptor recycling and degradation. Endosomal trafficking involving the sorting and compartmentalizing of different signals, which are subsequently distributed to the appropriate cellular destination, can at least partially explain how neurotrophins generate a diverse array of signalling outcomes. Although signalling endosomes provide a useful model for understanding how different cell surface receptor-mediated signals are generated and transported, the precise role, identity and functional definition of a signalling endosome remains unclear. In this review we will discuss the regulation of local versus long-range neurotrophin signalling, with a specific focus on recent developments in the role of endosomes in regulating the fate of Trk receptors.
Keywords
PI3KGIPCPhospholipase C gammaMVBNT-4NT-3EEA1PLCγAP-2GSK3p75NTRRac1NGFV-ATPaseCREBERK5BDNFERK1/2Vacuolar-type H+-ATPaseMAPKearly endosomal antigen 1multi-vesicular bodyTrkReceptor internalizationRas-related C3 botulinum toxin substrate 1nerve growth factorBrain-derived neurotrophic factorphosphatidylinositide 3-kinaseNeurotrophinsNeurotrophin 3Neurotrophin 4cAMP response element-binding proteinmitogen-activated protein kinaseextracellular signal-regulated kinase 1/2extracellular signal-regulated kinase 5glycogen synthase kinase 3p75 neurotrophin receptorTrk receptorstropomyosin receptor kinase
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Authors
Dusan Matusica, Elizabeth J. Coulson,