Insulin Induces Microtubule Stabilization and Regulates the Microtubule Plus-end Tracking Protein Network in Adipocytes
AuthorParker, Sara S
Barker, Natalie K
Deer, Chris G
Lee, Nam Y
Langlais, Paul R
AffiliationUniv Arizona, Coll Med, Dept Cellular & Mol Med
Univ Arizona, Coll Med, Dept Med, Div Endocrinol
Univ Arizona, Coll Med, Dept Pharmacol
Univ Arizona, Coll Med, Dept Chem & Biochem
Univ Arizona, Res Comp
MetadataShow full item record
CitationParker, S. S., Krantz, J., Kwak, E. A., Barker, N. K., Deer, C. G., Lee, N. Y., ... & Langlais, P. R. (2019). Insulin Induces Microtubule Stabilization and Regulates the Microtubule Plus-End Tracking Protein Network in Adipocytes. Molecular & Cellular Proteomics, mcp-RA119.
JournalMOLECULAR & CELLULAR PROTEOMICS
Rights© 2019 Parker et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractInsulin-stimulated glucose uptake is known to involve microtubules, although the function of microtubules and the microtubule-regulating proteins involved in insulin action are poorly understood. CLASP2, a plus-end tracking microtubule-associated protein (+TIP) that controls microtubule dynamics, was recently implicated as the first +TIP associated with insulin-regulated glucose uptake. Here, using protein-specific targeted quantitative phosphoproteomics within 3T3-L1 adipocytes, we discovered that insulin regulates phosphorylation of the CLASP2 network members G2L1, MARK2, CLIP2, AGAP3, and CKAP5 as well as EB1, revealing the existence of a previously unknown microtubule-associated protein system that responds to insulin. To further investigate, G2L1 interactome studies within 3T3-L1 adipocytes revealed that G2L1 coimmunoprecipitates CLASP2 and CLIP2 as well as the master integrators of +TIP assembly, the end binding (EB) proteins. Live-cell total internal reflection fluorescence microscopy in adipocytes revealed G2L1 and CLASP2 colocalize on microtubule plus-ends. We found that although insulin increases the number of CLASP2-containing plus-ends, insulin treatment simultaneously decreases CLASP2-containing plus-end velocity. In addition, we discovered that insulin stimulates redistribution of CLASP2 and G2L1 from exclusive plus-end tracking to "trailing" behind the growing tip of the microtubule. Insulin treatment increases alpha-tubulin Lysine 40 acetylation, a mechanism that was observed to be regulated by a counterbalance between GSK3 and mTOR, and led to microtubule stabilization. Our studies introduce insulin-stimulated microtubule stabilization and plus-end trailing of +TIPs as new modes of insulin action and reveal the likelihood that a network of microtubule-associated proteins synergize to coordinate insulin-regulated microtubule dynamics.
VersionFinal accepted manuscript
SponsorsTRIF Space Exploration and Optical Sciences (TRIF-SEOS) grant
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