High-resolution imaging demonstrates dynein-based vesicular transport of activated Trk receptors.
Target-derived neurotrophins signal from nerve endings to the cell body to influence cellular and nuclear responses. The retrograde signal is conveyed by neurotrophin receptors (Trks) themselves. To accomplish this, activated Trks may physically relocalize from nerve endings to the cell bodies. However, alternative signaling mechanisms may also be used. To identify the vehicle wherein the activated Trks are located and transported, and to identify associated motor proteins that would facilitate transport, we use activation-state specific antibodies in concert with immunoelectron microscopy and deconvolution microscopy. We show that the'activated Trks within rat sciatic nerve axons are preferentially localized to coated and uncoated vesicles. These vesicles are moving in a retrograde direction and so accumulate distal to a ligation site. The P-Trk containing vesicles, in turn, colocalize with dynein components, and not with kinesins. Collectively, these results indicate activated Trk within axons travel in vesicles and dynein is the motor that drives these vesicles towards the cell bodies.
Bhattacharyya
Anita
A
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Watson
Fiona L
FL
Pomeroy
Scott L
SL
Zhang
Yanzhen Z
YZ
Stiles
Charles D
CD
Segal
Rosalind A
RA
D016475:3T3 Cells; D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D004398:Dyneins / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D016547:Kinesins / Q000378:metabolism; D008297:Male; D051379:Mice; D016253:Microscopy, Immunoelectron; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D016716:PC12 Cells; D010748:Phosphopeptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D012584:Sciatic Nerve / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D018992:Myelin-Associated Glycoprotein; D010748:Phosphopeptides; D017475:Receptors, Nerve Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor; D004398:Dyneins; D016547:Kinesins