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

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

CCSer2 gates dynein activity at the cell periphery

Open access
Zang, Juliana L., Gibson, Daytan, Zheng, Ann-Marie, Shi, Wanjing, Gillies, John P., Stein, Chris, Drerup, Catherine M., DeSantis, Morgan E.·2024·The Journal of Cell Biology
DOI 10.1101/2024.06.13.598865PMC PMC12013514

Preprint — published as 10.1083/jcb.202406153 · Paper page

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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 and of cultured human cells by facilitating the trafficking of cargos that are acted on by cortically localized dynein. CCSer2 inhibits the interaction between dynein and its regulator Ndel1 exclusively at the cell periphery, resulting in localized dynein activation. Our findings suggest that the spatial specificity of dynein is achieved by the localization of proteins that disinhibit Ndel1. We propose that CCSer2 defines a broader class of proteins that activate dynein in distinct microenvironments via Ndel1 inhibition.

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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
The Journal of Cell Biology
Publisher
openRxiv
Published
2024-06-13
Volume
224
Issue
6
ISSN
0021-9525 (ISSN-L)
DOI
10.1101/2024.06.13.598865
PMC
PMC12013514
OpenAlex
W4409667805
Cited by
3
References
1
Citations by year
2026: 2 · 2025: 1
FWCI
1.50
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
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 Science Foundation (2142670)
  • National Institutes of Health
  • National Institute of General Medical Sciences (R00GM127757, R35GM146739, T32GM145304)
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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