Rab5 and Rab7 control endocytic sorting along the axonal retrograde transport pathway.
Vesicular pathways coupling the neuromuscular junction with the motor neuron soma are essential for neuronal function and survival. To characterize the organelles responsible for this long-distance crosstalk, we developed a purification strategy based on a fragment of tetanus neurotoxin (TeNT H(C)) conjugated to paramagnetic beads. This approach enabled us to identify, among other factors, the small GTPase Rab7 as a functional marker of a specific pool of axonal retrograde carriers, which transport neurotrophins and their receptors. Furthermore, Rab5 is essential for an early step in TeNT H(C) sorting but is absent from axonally transported vesicles. Our data demonstrate that TeNT H(C) uses a retrograde transport pathway shared with p75(NTR), TrkB, and BDNF, which is strictly dependent on the activities of both Rab5 and Rab7. Therefore, Rab7 plays an essential role in axonal retrograde transport by controlling a vesicular compartment implicated in neurotrophin traffic.
Deinhardt
Katrin
K
Molecular NeuroPathobiology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, United Kingdom.
Salinas
Sara
S
Verastegui
Carole
C
Watson
Rose
R
Worth
Daniel
D
Hanrahan
Sarah
S
Bucci
Cecilia
C
Schiavo
Giampietro
G
D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002451:Cell Compartmentation / Q000502:physiology; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000378:metabolism; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism; D009420:Nervous System / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D013744:Tetanus Toxin / Q000378:metabolism; D022161:Transport Vesicles / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins
D019208:Brain-Derived Neurotrophic Factor; D010446:Peptide Fragments; D020800:Receptor, Nerve Growth Factor; D013744:Tetanus Toxin; D000090802:rab7 GTP-Binding Proteins; C000716465:rab7 GTP-binding proteins, mouse; C040635:tetanus toxin fragment C; D020813:Receptor, trkB; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins