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Cited by 3Microtubule and mitosis dynamicsGenetic and Kidney Cyst DiseasesBiotin and Related Studies

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CCSer2 gates dynein activity at the cell periphery

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Zang, Juliana L., Gibson, Daytan, Zheng, Ann-Marie, Shi, Wanjing, Gillies, John P., Stein, Chris, Drerup, Catherine M., DeSantis, Morgan E.·2025·Journal of Cell Biology
DOI 10.1083/jcb.202406153PMC PMC12013514

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Abstract

Cytoplasmic dynein-1 (dynein) is a microtubule-associated, minus end–directed motor that traffics hundreds of different cargos. Dynein must discriminate between cargos and traffic them at the appropriate time from the correct cellular region. How dynein’s trafficking activity is regulated in time or cellular space remains poorly understood. Here, we identify CCSer2 as the first known protein to gate dynein activity in the spatial dimension. CCSer2 promotes the migration of developing zebrafish primordium cells, macrophages, and cultured human cells by facilitating the trafficking of cargos that are acted on by peripherally localized dynein. Our data suggest that CCSer2 disfavors the interaction between dynein and its regulator Ndel1 at the cell edge, resulting in localized dynein activation. These findings support a model where the spatial specificity of dynein is achieved by the localization of proteins that trigger Ndel1’s release from dynein. We propose that CCSer2 defines a broader class of proteins that activate dynein in distinct microenvironments via regulating Ndel1–dynein interaction.

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Metadata

Authors
Zang, J. L., Gibson, D., Zheng, A.-M., Shi, W., Gillies, J. P., Stein, C., Drerup, C. M., & DeSantis, M. E.
Affiliations
  • University of Michigan (US)
  • University of Wisconsin–Madison (US)
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2025-04-22
Volume
224
Issue
6
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.202406153
PMC
PMC12013514
OpenAlex
W4409667805
Cited by
3
References
3
Citations by year
2026: 2 · 2025: 1
FWCI
1.50
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Cell Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • National Institutes of Health (R35GM146739, R00GM127757, T32 GM145304)
  • National Science Foundation (2142670)
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 › Biotin and Related Studies
Keywords
cytoplasmic dynein-1, Ndel1, dynein activation, cell periphery, cargo trafficking, cell migration, macrophages, microtubule motor proteins

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