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Cited by 192Microtubule and mitosis dynamicsCellular Mechanics and InteractionsNeurogenesis and neuroplasticity mechanisms

Par3 and dynein associate to regulate local microtubule dynamics and centrosome orientation during migration.

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Schmoranzer, Jan, Fawcett, James P., Segura, Miriam, Tan, Serena, Vallee, Richard B., Pawson, Tony, Gundersen, Gregg G.·2009·Current Biology
DOI 10.1016/j.cub.2009.05.065PMC PMC2749750
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Abstract

Background Centrosome orientation toward the leading edge of migrating cells depends on dynein and microtubules (MTs), as well as a number of signaling factors at the leading edge. However, centrosomes are maintained at the cell center during orientation in fibroblasts, suggesting that factors working at sites other than the leading edge may also be involved. Results In a search for factors that function with dynein in centrosome orientation, we found that the polarity protein Par3 associated with dynein and that knockdown of Par3 inhibited centrosome orientation by disrupting the position of the centrosome at the cell center; this disrupted centrosome positioning is the same phenotype as that observed with dynein inhibition. Par3 associated with dynein through its N-terminal dimerization and PDZ1 domains and interacted specifically with dynein light intermediate chain 2 (LIC2). siRNA knockdown of LIC2, but not LIC1, or overexpression of LIC2 or the N-terminal domain of Par3, also inhibited centrosome orientation by disrupting centrosome position. In wound-edge fibroblasts, Par3 specifically localized to cell-cell contacts where it overlapped with MT ends and dynein puncta in a LIC2-dependent fashion. Live imaging showed that MTs exhibited increased pausing at cell-cell contacts compared to the leading edge and that this elevated pausing was dependent on Par3 and LIC2. Conclusions Par3 associates with dynein and contributes to the local regulation of MT dynamics at cell-cell contacts and proper positioning of the centrosome at the cell center. We propose that Par3 acts as a cortical factor that tethers MTs through its association with LIC2 dynein.

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  • Par3 interacts not only with KIF3A but also with the dynein subunit Dlic2.

    “Par3 interacts not only with KIF3A but also with the dynein subunit Dlic2 (Schmoranzer et al., 2009).”

    From Rassf5 and Ndr kinases act in a novel pathway regulating neuronal polarity through Par3 phosphorylation (2014) · cites this paper as Schmoranzer et al., 2009

    The Results section, “Par3 associates with dynein” (page unavailable), reports that dynein light intermediate chain 2 (LIC2) co-immunoprecipitated with Par3, supporting the Dlic2 portion of the claim. Our copy does not establish the claimed interaction between Par3 and KIF3A; searches for KIF3A found no relevant passage. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Ndr kinases and Par3 have been implicated in the regulation of centrosome duplication and orientation, respectively.

    “Ndr kinases and Par3 have been implicated in the regulation of centrosome duplication and orientation, respectively (Hergovich et al., 2007; Schmoranzer et al., 2009).”

    From Rassf5 and Ndr kinases act in a novel pathway regulating neuronal polarity through Par3 phosphorylation (2014) · cites this paper as Schmoranzer et al., 2009

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Authors
Schmoranzer, J., Fawcett, J. P., Segura, M., Tan, S., Vallee, R. B., Pawson, T., & Gundersen, G. G.
Affiliations
  • Columbia University (US)
  • Dalhousie University (CA)
  • Mount Sinai Hospital (CA)
Corresponding author
Gundersen, Gregg G.
ORCID
Venue
Current Biology
Publisher
Elsevier BV
Published
2009-07
Volume
19
Issue
13
Pages
1065-1074
ISSN
0960-9822 (ISSN-L)
DOI
10.1016/j.cub.2009.05.065
PMC
PMC2749750
OpenAlex
W2089693405
Cited by
192
References
2
Citations by year
2026: 2 · 2025: 7 · 2024: 8 · 2023: 12 · 2022: 2 · 2021: 7 · 2020: 9 · 2019: 18 · 2018: 10 · 2017: 6 · 2016: 10 · 2015: 16 · 2014: 26 · 2013: 12 · 2012: 13
FWCI
6.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute
  • National Institute of General Medical Sciences (GM 47434, R01GM047434, R37GM047434, R01GM062938, R01GM062939, GM062939)
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 › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
Par3, dynein, microtubule dynamics, cell migration, cell-cell contact, cell polarity, PDZ domain
MeSH terms
Animals, Cell Movement, Dyneins, Intercellular Junctions, Microtubules, Recombinant Fusion Proteins, Tubulin, Cell Adhesion Molecules, Centrosome, Cell Cycle Proteins, RNA, Small Interfering, NIH 3T3 Cells, Adaptor Proteins, Signal Transducing, Mice

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