A neuron-specific cytoplasmic dynein isoform preferentially transports TrkB signaling endosomes.
Cytoplasmic dynein is the multisubunit motor protein for retrograde movement of diverse cargoes to microtubule minus ends. Here, we investigate the function of dynein variants, defined by different intermediate chain (IC) isoforms, by expressing fluorescent ICs in neuronal cells. Green fluorescent protein (GFP)-IC incorporates into functional dynein complexes that copurify with membranous organelles. In living PC12 cell neurites, GFP-dynein puncta travel in both the anterograde and retrograde directions. In cultured hippocampal neurons, neurotrophin receptor tyrosine kinase B (TrkB) signaling endosomes are transported by cytoplasmic dynein containing the neuron-specific IC-1B isoform and not by dynein containing the ubiquitous IC-2C isoform. Similarly, organelles containing TrkB isolated from brain by immunoaffinity purification also contain dynein with IC-1 but not IC-2 isoforms. These data demonstrate that the IC isoforms define dynein populations that are selectively recruited to transport distinct cargoes.
Department of Cell Biology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Junghoon
J
Ha
Kevin W-H
KW
Lo
Kenneth R
KR
Myers
Tiffany M
TM
Carr
Michael K
MK
Humsi
Bareza A
BA
Rasoul
Rosalind A
RA
Segal
K Kevin
KK
Pfister
D000818:Animals; D002478:Cells, Cultured; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism*; D011992:Endosomes / Q000187:drug effects / Q000201:enzymology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007700:Kinetics; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009928:Organ Specificity / Q000187:drug effects; D016716:PC12 Cells; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D009414:Nerve Growth Factors; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D020917:Receptor, trkA; D020813:Receptor, trkB; D004398:Dyneins