Microtubule Destabilizer KIF2A Undergoes Distinct Site-Specific Phosphorylation Cascades that Differentially Affect Neuronal Morphogenesis

Cell Reports
Tadayuki Ogawa, Nobutaka Hirokawa

Abstract

Neurons exhibit dynamic structural changes in response to extracellular stimuli. Microtubules (MTs) provide rapid and dramatic cytoskeletal changes within the structural framework. However, the molecular mechanisms and signaling networks underlying MT dynamics remain unknown. Here, we have applied a comprehensive and quantitative phospho-analysis of the MT destabilizer KIF2A to elucidate the regulatory mechanisms of MT dynamics within neurons in response to extracellular signals. Interestingly, we identified two different sets of KIF2A phosphorylation profiles that accelerate (A-type) and brake (B-type) the MT depolymerization activity of KIF2A. Brain-derived neurotrophic factor (BDNF) stimulates PAK1 and CDK5 kinases, which decrease the MT depolymerizing activity of KIF2A through B-type phosphorylation, resulting in enhanced outgrowth of neural processes. In contrast, lysophosphatidic acid (LPA) induces ROCK2 kinase, which suppresses neurite outgrowth from round cells via A-type phosphorylation. We propose that these two mutually exclusive forms of KIF2A phosphorylation differentially regulate neuronal morphogenesis during development.

References

Dec 1, 1992·The Journal of Cell Biology·H AizawaN Hirokawa
Feb 16, 1999·Cell·A DesaiC E Walczak
Jun 21, 2001·Proceedings of the National Academy of Sciences of the United States of America·H MikiN Hirokawa
Feb 13, 2002·Current Biology : CB·Francis P G van HorckNullin Divecha
May 2, 2002·Molecular Cell·Carolyn A MooresRonald A Milligan
Jun 5, 2003·Nature Reviews. Molecular Cell Biology·Kirsi Riento, Anne J Ridley
Mar 19, 2004·The EMBO Journal·Krista ShipleyRobert Fletterick
Oct 14, 2004·The Journal of Cell Biology·Carolyn J LawrenceLinda Wordeman
Mar 8, 2007·PLoS Biology·Zelda H CheungNancy Y Ip
Aug 25, 2010·The Journal of Cell Biology·Tobias C Walther, Matthias Mann

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Citations

Feb 23, 2018·Cellular and Molecular Life Sciences : CMLS·Serene S L GweeRoger S Chung
May 2, 2019·Cellular and Molecular Life Sciences : CMLS·Oscar SeiraWolfram Tetzlaff
Mar 21, 2020·Journal of Neurochemistry·Aleksandra TempesJacek Jaworski
Oct 9, 2019·Life Science Alliance·Manabu ToyoshimaNobutaka Hirokawa
Apr 30, 2017·Cellular and Molecular Life Sciences : CMLS·Alina GoldsteinLarisa Gheber
Nov 30, 2016·Molecular Genetics & Genomic Medicine·Guoling TianEthan M Goldberg
Dec 6, 2017·Biophysics Reviews·Tadayuki Ogawa, Nobutaka Hirokawa
Jan 16, 2021·Cells·Nadine F JosephSathyanarayanan V Puthanveettil
Nov 6, 2017·Trends in Genetics : TIG·Colleen N McLaughlin, Heather T Broihier
Jun 18, 2021·The Journal of Cell Biology·Dharmendra PuriAnindya Ghosh-Roy
Aug 22, 2021·Proceedings of the National Academy of Sciences of the United States of America·Anja BufeSergio P Acebrón

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