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A PIK3C3-ankyrin-B-dynactin pathway promotes axonal growth and multiorganelle transport.

Publication ,  Journal Article
Lorenzo, DN; Badea, A; Davis, J; Hostettler, J; He, J; Zhong, G; Zhuang, X; Bennett, V
Published in: J Cell Biol
December 22, 2014

Axon growth requires long-range transport of organelles, but how these cargoes recruit their motors and how their traffic is regulated are not fully resolved. In this paper, we identify a new pathway based on the class III PI3-kinase (PIK3C3), ankyrin-B (AnkB), and dynactin, which promotes fast axonal transport of synaptic vesicles, mitochondria, endosomes, and lysosomes. We show that dynactin associates with cargo through AnkB interactions with both the dynactin subunit p62 and phosphatidylinositol 3-phosphate (PtdIns(3)P) lipids generated by PIK3C3. AnkB knockout resulted in shortened axon tracts and marked reduction in membrane association of dynactin and dynein, whereas it did not affect the organization of spectrin-actin axonal rings imaged by 3D-STORM. Loss of AnkB or of its linkages to either p62 or PtdIns(3)P or loss of PIK3C3 all impaired organelle transport and particularly retrograde transport in hippocampal neurons. Our results establish new functional relationships between PIK3C3, dynactin, and AnkB that together promote axonal transport of organelles and are required for normal axon length.

Duke Scholars

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Published In

J Cell Biol

DOI

EISSN

1540-8140

Publication Date

December 22, 2014

Volume

207

Issue

6

Start / End Page

735 / 752

Location

United States

Related Subject Headings

  • Organelles
  • Microtubules
  • Microtubule-Associated Proteins
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice, 129 Strain
  • Male
  • Hippocampus
  • Female
  • Dynactin Complex
 

Citation

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Chicago
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Lorenzo, D. N., Badea, A., Davis, J., Hostettler, J., He, J., Zhong, G., … Bennett, V. (2014). A PIK3C3-ankyrin-B-dynactin pathway promotes axonal growth and multiorganelle transport. J Cell Biol, 207(6), 735–752. https://doi.org/10.1083/jcb.201407063
Lorenzo, Damaris Nadia, Alexandra Badea, Jonathan Davis, Janell Hostettler, Jiang He, Guisheng Zhong, Xiaowei Zhuang, and Vann Bennett. “A PIK3C3-ankyrin-B-dynactin pathway promotes axonal growth and multiorganelle transport.J Cell Biol 207, no. 6 (December 22, 2014): 735–52. https://doi.org/10.1083/jcb.201407063.
Lorenzo DN, Badea A, Davis J, Hostettler J, He J, Zhong G, et al. A PIK3C3-ankyrin-B-dynactin pathway promotes axonal growth and multiorganelle transport. J Cell Biol. 2014 Dec 22;207(6):735–52.
Lorenzo, Damaris Nadia, et al. “A PIK3C3-ankyrin-B-dynactin pathway promotes axonal growth and multiorganelle transport.J Cell Biol, vol. 207, no. 6, Dec. 2014, pp. 735–52. Pubmed, doi:10.1083/jcb.201407063.
Lorenzo DN, Badea A, Davis J, Hostettler J, He J, Zhong G, Zhuang X, Bennett V. A PIK3C3-ankyrin-B-dynactin pathway promotes axonal growth and multiorganelle transport. J Cell Biol. 2014 Dec 22;207(6):735–752.

Published In

J Cell Biol

DOI

EISSN

1540-8140

Publication Date

December 22, 2014

Volume

207

Issue

6

Start / End Page

735 / 752

Location

United States

Related Subject Headings

  • Organelles
  • Microtubules
  • Microtubule-Associated Proteins
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice, 129 Strain
  • Male
  • Hippocampus
  • Female
  • Dynactin Complex