Cited by 58Microtubule and mitosis dynamicsCellular Mechanics and InteractionsGenetic and Kidney Cyst Diseases

Microtubule-associated protein MAP7 promotes tubulin posttranslational modifications and cargo transport to enable osmotic adaptation

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Shen, Yusheng, Ori-McKenney, Kassandra M.·2024·Developmental Cell

Abstract

Cells remodel their cytoskeletal networks to adapt to their environment. Here, we analyze the mechanisms utilized by the cell to tailor its microtubule landscape in response to changes in osmolarity that alter macromolecular crowding. By integrating live-cell imaging, ex vivo enzymatic assays, and in vitro reconstitution, we probe the impact of cytoplasmic density on microtubule-associated proteins (MAPs) and tubulin posttranslational modifications (PTMs). We find that human epithelial cells respond to fluctuations in cytoplasmic density by modulating microtubule acetylation, detyrosination, or MAP7 association without differentially affecting polyglutamylation, tyrosination, or MAP4 association. These MAP-PTM combinations alter intracellular cargo transport, enabling the cell to respond to osmotic challenges. We further dissect the molecular mechanisms governing tubulin PTM specification and find that MAP7 promotes acetylation and inhibits detyrosination. Our data identify MAP7 in modulating the tubulin code, resulting in microtubule cytoskeleton remodeling and alteration of intracellular transport as an integrated mechanism of cellular adaptation.

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Research works printed but not linked: 11

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Authors
Shen, Y., & Ori-McKenney, K. M.
Affiliations
University of California, Davis (US)
Corresponding author
Ori-McKenney, Kassandra M.
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2024-06
Volume
59
Issue
12
Pages
1553-1570.e7
ISSN
1534-5807 (ISSN-L)
OpenAlex
W4393899203
Cited by
58
References
8
Citations by year
2026: 30 · 2025: 22 · 2024: 6
FWCI
12.30
Type
journal article
Language
en
Open access
Locations
  • Developmental Cell (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • National Institutes of Health (VASH1-SVBP)
  • University of Oregon
  • NIGMS (1R35GM133688)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
Keywords
MAP7, tubulin post-translational modifications, microtubule acetylation, tubulin detyrosination, microtubule-associated proteins, osmoadaptation, macromolecular crowding, cytoplasmic density, intracellular cargo transport, epithelial cells, MAP4, tubulin code

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