Dynein-dynactin segregate meiotic chromosomes in C. elegans spermatocytes.

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.

• Authors: Daniel J Barbosa, Vanessa Teixeira, Joana Duro, Ana X Carvalho, Reto Gassmann
• Journal: Development (Cambridge, England) (Development) Vol. 148 Issue 3 (02 10 2021) ISSN: 1477-9129 [Electronic] England
• PMID: 33462114 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. Published by The Company of Biologists Ltd.

Chemical References

• DCTN1 protein, human
• Dynactin Complex
• Cytoplasmic Dyneins
• Dyneins

Topics

• Animals
• Caenorhabditis elegans (metabolism)
• Chromosome Segregation
• Chromosomes
• Cytoplasmic Dyneins (metabolism)
• Dynactin Complex (genetics, metabolism)
• Dyneins (metabolism)
• Female
• Humans
• Male
• Meiosis
• Mitosis
• Muscular Atrophy, Spinal (genetics, metabolism)
• Mutation
• Spermatocytes (metabolism)
• Spindle Apparatus (metabolism)