Handling Editor: Swathi Arur
ABSTRACT
The microtubule motor cytoplasmic dynein 1 (dynein) and its essential activator dynactin have conserved roles in spindle assembly and positioning during female meiosis and mitosis, but their contribution to male meiosis remains poorly understood. Here, we characterize the G33S mutation in the C. elegans dynactin subunit DNC-1, which corresponds to G59S in human p150Glued that causes motor neuron disease. In spermatocytes, dnc-1(G33S) delays spindle assembly and penetrantly inhibits anaphase spindle elongation in meiosis I, which prevents the segregation of homologous chromosomes. By contrast, chromosomes segregate without errors in the early dnc-1(G33S) embryo. Deletion of the DNC-1 N-terminus shows that defective meiosis in dnc-1(G33S) spermatocytes is not due to the inability of DNC-1 to interact with microtubules. Instead, our results suggest that the DNC-1(G33S) protein, which is aggregation prone in vitro, is less stable in spermatocytes than the early embryo, resulting in different phenotypic severity in the two dividing tissues. Thus, the dnc-1(G33S) mutant reveals that dynein-dynactin drive meiotic chromosome segregation in spermatocytes and illustrates that the extent to which protein misfolding leads to loss of function can vary significantly between cell types.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: D.J.B., A.X.C., R.G.; Methodology: D.J.B.; Validation: D.J.B., R.G.; Formal analysis: D.J.B., V.T., J.D., R.G.; Investigation: D.J.B., V.T., J.D.; Resources: A.X.C., R.G.; Writing - original draft: D.J.B., A.X.C., R.G.; Writing - review & editing: D.J.B., A.X.C., R.G.; Visualization: D.J.B., R.G.; Supervision: D.J.B., A.X.C., R.G.; Project administration: R.G.; Funding acquisition: R.G.
Funding
This study was financed by the Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Ensino Superior (PTDC/BIA-CEL/30507/2017). R.G. and A.X.C. are supported by FCT Principal Investigator positions (CEECIND/00333/2017 and CEECIND/01967/2017, respectively), and D.J.B. is supported by a Fundação para a Ciência e a Tecnologia Junior Researcher position (DL57/2016/CP1355/CT0007).
Supplementary information
Supplementary information available online at https://dev.biologists.org/lookup/doi/10.1242/dev.197780.supplemental
- Received October 19, 2020.
- Accepted January 5, 2021.
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