Posttranslational Modifications of Tubulin and the Polarized Transport of Kinesin-1 in Neurons

Molecular Biology of the Cell - Tập 21 Số 4 - Trang 572-583 - 2010
Jennetta W. Hammond1, Chun-Fang Huang2, Stefanie Kaech2, Catherine Jacobson2,3, Gary Banker2, Kristen J. Verhey1
1*Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109; and
2Jungers Center for Neurosciences Research, Oregon Health and Science University, Portland, OR 97239
3University of California at San Francisco

Tóm tắt

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 3β 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.

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