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Retrograde neurotrophin signalling
Stable Identifier
R-HSA-177504
DOI
10.3180/REACT_12435.1
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Signal Transduction (Homo sapiens)
Signaling by Receptor Tyrosine Kinases (Homo sapiens)
Signaling by NTRKs (Homo sapiens)
Signaling by NTRK1 (TRKA) (Homo sapiens)
Retrograde neurotrophin signalling (Homo sapiens)
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Neurotrophin-TRK complexes can be internalized and enter signalling vesicles, which travel retrogradely over long distances from distal nerve terminals to neuronal cell bodies. Such retrograde signalling by neurotrophin-TRK complexes regulates survival, synaptogenesis and maintenance of proper neural connectivity. The neurotrophin-TRK complex may use three distinct internalization pathways. Although Clathrin-mediated endocytosys appears to be the major internalization route, it is controversial whether it also represents the dominant pathway for retrograde transport and signalling. Pyncher-mediated endocytosis might be more relevant in this regard. Moreover, also caveolin-mediated endocytosis may play a role in NGF-TrkA internalization.
Retrograde transport of TRKs is microtubule-dependent: TRKs remain activated and bound to neurotrophins during retrograde transport. The current view is reflected in the signalling endosome model. It is a specialized vesicle containing ligand (NGF, BDNF) bound to its activated TRK receptor, together with activated downstream signalling proteins, transported by motor proteins (dyneins) from nerve terminals to remote cell bodies, where the receptors trigger signalling cascades.
Participants
Events
Formation of clathrin-coated vesicle
(Homo sapiens)
Endocytosis (internalization) of clathrin-coated vesicle
(Homo sapiens)
Axonal transport of NGF:Trk complexes
(Homo sapiens)
Participates
as an event of
Signaling by NTRK1 (TRKA) (Homo sapiens)
Orthologous Events
Retrograde neurotrophin signalling (Bos taurus)
Retrograde neurotrophin signalling (Canis familiaris)
Retrograde neurotrophin signalling (Drosophila melanogaster)
Retrograde neurotrophin signalling (Gallus gallus)
Retrograde neurotrophin signalling (Mus musculus)
Retrograde neurotrophin signalling (Rattus norvegicus)
Retrograde neurotrophin signalling (Sus scrofa)
Authored
Nasi, S (2006-10-10)
Annibali, D (2006-10-10)
Reviewed
Greene, LA (2007-11-08)
Created
Jassal, B (2006-03-31)
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