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Cited by 44Microtubule and mitosis dynamicsGenetic and Kidney Cyst Diseasesmelanin and skin pigmentation

Regulation of microtubule-based transport by MAP4

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Semenova, Irina, Ikeda, Kazuho, Resaul, Karim, Kraikivski, Pavel, Aguiar, Mike, Gygi, Steven, Zaliapin, Ilya, Cowan, Ann +1 more·2014·Molecular Biology of the Cell
DOI 10.1091/mbc.e14-01-0022PMC PMC4196864
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Abstract

Microtubule (MT)-based transport of organelles driven by the opposing MT motors kinesins and dynein is tightly regulated in cells, but the underlying molecular mechanisms remain largely unknown. Here we tested the regulation of MT transport by the ubiquitous protein MAP4 using Xenopus melanophores as an experimental system. In these cells, pigment granules (melanosomes) move along MTs to the cell center (aggregation) or to the periphery (dispersion) by means of cytoplasmic dynein and kinesin-2, respectively. We found that aggregation signals induced phosphorylation of threonine residues in the MT-binding domain of the Xenopus MAP4 (XMAP4), thus decreasing binding of this protein to MTs. Overexpression of XMAP4 inhibited pigment aggregation by shortening dynein-dependent MT runs of melanosomes, whereas removal of XMAP4 from MTs reduced the length of kinesin-2–dependent runs and suppressed pigment dispersion. We hypothesize that binding of XMAP4 to MTs negatively regulates dynein-dependent movement of melanosomes and positively regulates kinesin-2–based movement. Phosphorylation during pigment aggregation reduces binding of XMAP4 to MTs, thus increasing dynein-dependent and decreasing kinesin-2–dependent motility of melanosomes, which stimulates their accumulation in the cell center, whereas dephosphorylation of XMAP4 during dispersion has an opposite effect.

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  • The modest effect of MAP4 on the DDH landing rate may be consistent with prior results suggesting MAP4 could inhibit dynein-based movements.

    “The modest effect of MAP4 on the DDH landing rate may be consistent with prior results18,19, which suggested MAP4 could inhibit dynein-based movements.”

    From Microtubule lattice spacing governs cohesive envelope formation of tau family proteins (2022) · cites this paper as [18]

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Authors
Semenova, I., Ikeda, K., Resaul, K., Kraikivski, P., Aguiar, M., Gygi, S., Zaliapin, I., Cowan, A., & Rodionov, V.
Affiliations
  • UConn Health (US)
  • RIKEN (JP)
  • Harvard University (US)
  • University of Nevada, Reno (US)
Corresponding author
Rodionov, Vladimir
ORCID
Venue
Molecular Biology of the Cell
Publisher
American Society for Cell Biology (ASCB)
Published
2014-10-15
Volume
25
Issue
20
Pages
3119-3132
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
DOI
10.1091/mbc.e14-01-0022
PMC
PMC4196864
OpenAlex
W2123272295
Cited by
44
References
5
Citations by year
2026: 2 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 7 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 3 · 2015: 2
FWCI
1.69
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • Molecular Biology of the Cell (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
  • National Institutes of Health
  • Japan Society for the Promotion of Science (25293046, 26440108)
  • National Institute of General Medical Sciences (GM-62290, P41GM103313, R01GM062290)
  • National Center for Research Resources (P41RR013186)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
Keywords
MAP4, microtubule transport, melanosomes, pigment dispersion, cytoplasmic dynein, kinesin-2, threonine phosphorylation, microtubule binding
MeSH terms
Animals, Biological Transport, Cell Line, Dyneins, Melanophores, Microtubule-Associated Proteins, Microtubules, Phosphorylation, Xenopus, Kinesins, Melanosomes, Xenopus Proteins

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