Microtubule acetylation promotes kinesin-1 binding and transport.
Long-distance intracellular delivery is driven by kinesin and dynein motor proteins that ferry cargoes along microtubule tracks . Current models postulate that directional trafficking is governed by known biophysical properties of these motors-kinesins generally move to the plus ends of microtubules in the cell periphery, whereas cytoplasmic dynein moves to the minus ends in the cell center. However, these models are insufficient to explain how polarized protein trafficking to subcellular domains is accomplished. We show that the kinesin-1 cargo protein JNK-interacting protein 1 (JIP1) is localized to only a subset of neurites in cultured neuronal cells. The mechanism of polarized trafficking appears to involve the preferential recognition of microtubules containing specific posttranslational modifications (PTMs) by the kinesin-1 motor domain. Using a genetic approach to eliminate specific PTMs, we show that the loss of a single modification, alpha-tubulin acetylation at Lys-40, influences the binding and motility of kinesin-1 in vitro. In addition, pharmacological treatments that increase microtubule acetylation cause a redirection of kinesin-1 transport of JIP1 to nearly all neurite tips in vivo. These results suggest that microtubule PTMs are important markers of distinct microtubule populations and that they act to control motor-protein trafficking.
Reed
Nathan A
NA
Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.
Cai
Dawen
D
Blasius
T Lynne
TL
Jih
Gloria T
GT
Meyhofer
Edgar
E
Gaertig
Jacek
J
Verhey
Kristen J
KJ
D000107:Acetylation; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis; D019556:COS Cells; D002522:Chlorocebus aethiops; D004330:Drosophila; D004398:Dyneins / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008164:Luminescent Proteins / Q000032:analysis; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D013768:Tetrahymena / Q000737:chemistry; D014404:Tubulin / Q000737:chemistry / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D001426:Bacterial Proteins; D008164:Luminescent Proteins; C490665:Mapk8ip protein, mouse; D014404:Tubulin; C054562:yellow fluorescent protein, Bacteria; D004398:Dyneins; D016547:Kinesins