Posttranslational modifications of tubulin and the polarized transport of kinesin-1 in neurons.
Polarized transport by microtubule-based motors is critical for neuronal development and function. Selective translocation of the Kinesin-1 motor domain is the earliest known marker of axonal identity, occurring before morphological differentiation. Thus, Kinesin-1-mediated transport may contribute to axonal specification. We tested whether posttranslational modifications of tubulin influence the ability of Kinesin-1 motors to distinguish microtubule tracks during neuronal development. We detected no difference in microtubule stability between axons and minor neurites in polarized stage 3 hippocampal neurons. In contrast, microtubule modifications were enriched in a subset of neurites in unpolarized stage 2 cells and the developing axon in polarized stage 3 cells. This enrichment correlated with the selective accumulation of constitutively active Kinesin-1 motors. Increasing tubulin acetylation, without altering the levels of other tubulin modifications, did not alter the selectivity of Kinesin-1 accumulation in polarized cells. However, globally enhancing tubulin acetylation, detyrosination, and polyglutamylation by Taxol treatment or inhibition of glycogen synthase kinase 3beta decreased the selectivity of Kinesin-1 translocation and led to the formation of multiple axons. Although microtubule acetylation enhances the motility of Kinesin-1, the preferential translocation of Kinesin-1 on axonal microtubules in polarized neuronal cells is not determined by acetylation alone but is probably specified by a combination of tubulin modifications.
Hammond
Jennetta W
JW
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Huang
Chun-Fang
CF
Kaech
Stefanie
S
Jacobson
Catherine
C
Banker
Gary
G
Verhey
Kristen J
KJ
D000107:Acetylation; D000818:Animals; D016764:Cell Polarity; D002478:Cells, Cultured; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology
D020033:Protein Isoforms; D014404:Tubulin; D050257:Tubulin Modulators; D038362:Glycogen Synthase Kinase 3; D016547:Kinesins; D017239:Paclitaxel