Microtubule acetylation regulates dynamics of KIF1C-powered vesicles and contact of microtubule plus ends with podosomes

Eur J Cell Biol. 2014 Oct;93(10-12):424-37. doi: 10.1016/j.ejcb.2014.07.006. Epub 2014 Aug 2.

Abstract

Microtubule dynamics are important for a variety of key cellular functions such as intracellular trafficking, adjustment of the cell surface proteome, or adhesion structure turnover. In the current study, we investigate the effects of altered microtubule acetylation levels on the subcellular distribution of kinesins and actin cytoskeletal architecture in primary human macrophages. Microtubule acetylation was altered by overexpression or siRNA-induced depletion of the acetylase MEC-17, or by blocking α-tubulin deacetylation by addition of the inhibitor tubacin. We show that microtubule acetylation influences the subcellular distribution of vesicles associated with the kinesin KIF1C, as well as their directionality, velocity and run length. Moreover, tubulin acetylation alters the targeting frequency of microtubule plus ends on podosomes and influences the number of podosomes per cell and thus the matrix-degrading capacity of macrophages. Collectively, our results point to α-tubulin acetylation as an important modification that impacts on kinesin vesicle dynamics, actin cytoskeletal architecture and cellular function of macrophages.

Keywords: KIF1C; Kinesin; MEC-17; Macrophage; Microtubule acetylation; Podosomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism
  • Actin Cytoskeleton / metabolism
  • Anilides / pharmacology
  • Cell Surface Extensions / metabolism*
  • Histone Deacetylase Inhibitors / pharmacology
  • Humans
  • Hydroxamic Acids / pharmacology
  • Kinesin / metabolism*
  • Macrophages / metabolism
  • Microtubule Proteins
  • Microtubules / metabolism*
  • Primary Cell Culture
  • RNA, Small Interfering / metabolism
  • Transport Vesicles / metabolism*
  • Tubulin / metabolism

Substances

  • Anilides
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • KIF1C protein, human
  • Microtubule Proteins
  • RNA, Small Interfering
  • Tubulin
  • tubacin
  • Acetyltransferases
  • ATAT1 protein, human
  • Kinesin