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Regulation of microtubule-based transport by MAP4

Irina Semenova1, Kazuho Ikeda2, Karim Resaul1

  • 1R.D. Berlin Center for Cell Analysis and Modeling and Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030.

Molecular Biology of the Cell
|August 22, 2014
PubMed

Insights

Microtubule (MT) transport is regulated by MAP4. Phosphorylation of MAP4 alters its binding to MTs, controlling organelle movement via kinesin and dynein motors.

Area of Science:

  • Cell Biology
  • Molecular Motors
  • Cytoskeletal Dynamics

Background:

  • Microtubule (MT)-based organelle transport relies on opposing motors, kinesins and dynein.
  • The precise molecular mechanisms regulating this transport are not fully understood.

Purpose of the Study:

  • To investigate the role of Microtubule-Associated Protein 4 (MAP4) in regulating MT-based organelle transport.
  • To elucidate the molecular mechanisms controlling pigment granule (melanosome) movement in Xenopus melanophores.

Main Methods:

  • Utilized Xenopus melanophores as an experimental system to study MT transport.
  • Investigated the phosphorylation status and MT-binding affinity of Xenopus MAP4 (XMAP4).
  • Examined the effects of XMAP4 overexpression and removal on melanosome aggregation and dispersion.

Main Results:

  • Aggregation signals induced phosphorylation of XMAP4, reducing its binding to MTs.
  • Overexpression of XMAP4 inhibited pigment aggregation by shortening dynein-dependent MT runs.
  • Removal of XMAP4 from MTs reduced kinesin-2-dependent runs and suppressed pigment dispersion.

Conclusions:

  • MAP4 binding to MTs negatively regulates dynein-dependent melanosome movement and positively regulates kinesin-2-based movement.
  • Phosphorylation of XMAP4 during aggregation decreases its MT binding, promoting dynein activity and aggregation.
  • Dephosphorylation of XMAP4 during dispersion has the opposite effect, favoring kinesin-2 activity and dispersion.

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