Comparison of nerve terminal events in vivo effecting retrograde transport of vesicles containing neurotrophins or synaptic vesicle components.
Although vesicular retrograde transport of neurotrophins in vivo is well established, relatively little is known about the mechanisms that underlie vesicle endocytosis and formation before transport. We demonstrate that in vivo not all retrograde transport vesicles are alike, nor are they all formed using identical mechanisms. As characterized by density, there are at least two populations of vesicles present in the synaptic terminal that are retrogradely transported along the axon: those containing neurotrophins (NTs) and those resulting from synaptic vesicle recycling. Vesicles containing nerve growth factor (NGF), NT-3, or NT-4 had similar densities with peak values at about 1.05 g/ml. Synaptic-derived vesicles, labeled with anti-dopamine beta-hydroxylase (DBH), had densities with peak values at about 1.16 g/ml. We assayed the effects of pharmacologic agents in vivo on retrograde transport from the anterior eye chamber to the superior cervical ganglion. Inhibitors of phosphatidylinositol-3-OH (PI-3) kinase and actin function blocked transport of both anti-DBH and NGF, demonstrating an essential role for these molecules in retrograde transport of both vesicle types. Dynamin, a key element in synaptic vesicle recycling, was axonally transported in retrograde and anterograde directions, and compounds able to interfere with dynamin function had a differential effect on retrograde transport of NTs and anti-DBH. Okadaic acid significantly decreased retrograde axonal transport of anti-DBH and increased NGF retrograde transport. We conclude that there are both different and common proteins involved in endocytosis and targeting of retrograde transport of these two populations of vesicles.
Developmental Neurobiology Group, Division of Neuroscience, John Curtin School of Medical Research, ANU, Canberra, ACT, Australia.
M W
MW
Weible
N
N
Ozsarac
M L
ML
Grimes
I A
IA
Hendry
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001370:Axonal Transport / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western / Q000379:methods; D002395:Catecholamines / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000276:immunology / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007456:Iodine Isotopes / Q000378:metabolism; D008026:Ligation / Q000379:methods; D020932:Nerve Growth Factor / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D009532:Nickel / Q000494:pharmacology; D017933:Peripheral Nervous System / Q000166:cytology* / Q000502:physiology; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects; D013572:Synaptic Vesicles / Q000145:classification / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology
D000906:Antibodies; D002395:Catecholamines; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D007456:Iodine Isotopes; D009414:Nerve Growth Factors; D020032:Tyrphostins; D009532:Nickel; D020932:Nerve Growth Factor; D004299:Dopamine beta-Hydroxylase; D034281:Dynamins; D016559:Tacrolimus