Biology subjects

Dierlam, C.

Publications and source records attributed to Dierlam, C..

3 recordsLinked to original sources

bioRxiv2025

Dynamin regulates PLK-1 localization and spindle pole assembly during mitosis

Accurate mitosis is essential for genome stability. Although dynamin is best known for its role in vesicular trafficking, its functions during mitosis remain unclear. Here, we identify a mitotic role for the C. elegans dynamin homolog DYN-1 in regulating spindle assembly and the localization of the key mitotic regulators SPD-2 and PLK-1. Depletion of DYN-1 results in enlarged metaphase spindle poles and increased centrosomal SPD-2 and PLK-1 levels. These effects likely depend on DYN-1-mediated vesicular trafficking, as shown by assays with the dyn-1(ky51) allele. Additionally, a subset of DYN-1-depleted embryos exhibit altered PLK-1 localization at the midbody during late mitosis, correlating with midbody assembly defects. Together, these findings establish DYN-1 as a previously unrecognized regulator of spindle pole organization and early midbody assembly. SIGNIFICANCE STATEMENTDynamin is primarily known for its function in endocytosis, but its involvement in mitosis is not well defined. This study shows that dynamin helps organize mitotic spindle poles, ensures proper centrosome localization of SPD-2 and PLK-1, and supports early steps of midbody assembly in C. elegans embryos. These findings reveal a previously unrecognized mitotic role for dynamin and suggest new links between membrane dynamics, spindle organization, and the cytokinetic machinery.

cell biology↗

bioRxiv2022

A primary microcephaly-associated sas-6 mutation perturbs centrosome duplication and ciliogenesis in Caenorhabditis elegans

The human SASS6(I62T) missense mutation has been linked with the incidence of primary microcephaly in a Pakistani family, although the mechanisms by which this mutation causes disease remain unclear. The SASS6(I62T) mutation corresponds to SAS-6(L69T) in C. elegans. Given that SAS-6 is highly conserved, we modeled this mutation in C. elegans and examined sas-6(L69T) effect on centrosome duplication, ciliogenesis and dendrite morphogenesis. Our studies revealed that all the above processes are perturbed by the sas-6(L69T) mutation. Specifically, C. elegans carrying the sas-6(L69T) mutation exhibit an increased failure of centrosome duplication in a sensitized genetic background. Further, worms carrying this mutation also display shortened phasmid cilia, an abnormal phasmid cilia morphology, shorter phasmid dendrites and chemotaxis defects. Our data show that the centrosome duplication defects caused by this mutation are only uncovered in a sensitized genetic background, indicating that these defects are mild. However, the ciliogenesis and dendritic defects caused by this mutation are evident in an otherwise wild-type background, indicating that they are stronger defects. Thus, our studies shed light on the novel mechanisms by which the sas-6(L69T) mutation could contribute to the incidence of primary microcephaly in humans.

genetics↗

bioRxiv2021

The retromer complex regulates C. elegans development and mammalian ciliogenesis

The mammalian retromer is comprised of subunits VPS26, VPS29 and VPS35, and a more loosely-associated sorting nexin (SNX) heterodimer. Despite known roles for the retromer in multiple trafficking events in yeast and mammalian cells, its role in development is poorly understood, and its potential function in primary ciliogenesis remains unknown. Using CRISPR-Cas9 editing, we demonstrated that vps-26 homozygous knockout C. elegans have reduced brood sizes and impaired vulval development, as well as decreased body length which has been linked to defects in primary ciliogenesis. Since many endocytic proteins are implicated in the generation of primary cilia, we addressed whether the retromer regulates ciliogenesis in mammalian cells. We observed VPS35 localized to the primary cilium, and depletion of VPS26, VPS35 or SNX1/SNX5 led to decreased ciliogenesis. Retromer also coimmunoprecipitated with the capping protein, CP110, and was required for its removal from the mother centriole. Herein, we characterize new roles for the retromer in C. elegans development and in the regulation of ciliogenesis in mammalian cells, and suggest a novel role for the retromer in CP110 removal from the mother centriole.

cell biology↗