Biology subjects

Hübner, A.

Publications and source records attributed to Hübner, A..

3 recordsLinked to original sources

bioRxiv2018

Triple A patient cells suffering from mitotic defects fail to localize PGRMC1 to mitotic kinetochore fibers

HIGHLIGHT SUMMARYO_LIInvestigating cell division in human adrenal cells we show that proliferation is decreased upon overexpression of ALADIN, PGRMC1 or PGRMC2.\nC_LIO_LIIn immunofluorescence experiments using human adrenal cells and triple A patient fibroblasts we observed that during cell division PGRMC1 localizes to the microtubule kinetochore-fibers in metaphase and to the mid-body in telophase.\nC_LIO_LIDepletion of ALADIN results in mis-localization of Aurora A and PGRMC1 in metaphase cells of the human adrenal cell line and fibroblasts derived from patients with triple A syndrome.\nC_LIO_LIIn real time PCR using RNA of fibroblasts of triple A syndrome patients and healthy controls we measured an increased expression of PGRMC2 in cells with ALADIN mis-function compared to the control cells.\nC_LIO_LIWe hypothesize that a loss of the regulatory interaction between ALADIN and PGRMC2 leads to an over-regulation and over-expression of PGRMC2 and displaces PGRMC1 at the metaphase spindle. This diminishing of PGRMC1 concentration at kinetochore fibers may lead to mitotic errors and pro - liferation arrest.\nC_LI\n\nABSTRACTMembrane-associated progesterone receptors are restricted to the endoplasmic reticulum and are shown to regulate the activity of cytochrome P450 enzymes which are involved in steroidogenesis or drug detoxification. PGRMC1 and PGRMC2 belong to this group of microsomal receptors and are of interest due to their suspected role during cell cycle. PGRMC1 and PGRMC2 are thought to bind to each other thereby suppressing entry into mitosis. We could previously report that PGRMC2 interacts with the nucleoporin ALADIN which when mutated results in the autosomal recessive disorder triple A syndrome. ALADIN is a novel regulator of mitotic controller Aurora kinase A and depletion of this nucleoporin leads to microtubule instability. In the current study, we present that proliferation is decreased when ALADIN, PGRMC1 or PGRMC2 are over-expressed. Furthermore, we find that depletion of ALADIN results in mis-localization of Aurora kinase A and PGRMC1 in metaphase cells. Additionally, PGRMC2 is over-expressed in triple A patient fibroblasts. Our results emphasize the possibility that loss of the regulatory interaction between ALADIN and PGRMC2 gives rise to a depletion of PGRMC1 at kinetochore fibers and to mitotic errors. This observation may explain part of the symptoms seen in triple A syndrome patients.

cell biology↗

bioRxiv2018

The role of matrilineality in shaping patterns of Y chromosome and mtDNA sequence variation in southwestern Angola

Southwestern Angola is a region characterized by contact between indigenous foragers and incoming food-producers, involving genetic and cultural exchanges between peoples speaking Kxa, Khoe-Kwadi and Bantu languages. Although present-day Bantu-speakers share a patrilocal residence pattern and matrilineal principle of clan and group membership, a highly stratified social setting divides dominant pastoralists from marginalized groups that subsist on alternative strategies and have previously been though to have pre-Bantu origins. Here, we compare new high-resolution sequence data from 2.3 Mb of the non-recombining Y chromosome (NRY) from 170 individuals with previously reported mitochondrial genomes (mtDNA), to investigate the population history of seven representative southwestern Angolan groups (Himba, Kuvale, Kwisi, Kwepe, Twa, Tjimba, !Xun) and to study the causes and consequences of sex-biased processes in their genetic variation. We found no clear link between the formerly Kwadi-speaking Kwepe and pre-Bantu eastern African migrants, and no pre-Bantu NRY lineages among Bantu-speaking groups, except for small amounts of \"Khoisan\" introgression. We therefore propose that irrespective of their subsistence strategies, all Bantu-speaking groups of the area share a male Bantu origin. Additionally, we show that in Bantu-speaking groups, the levels of among-group and between-group variation are higher for mtDNA than for NRY. These results, together with our previous demonstration that the matriclanic systems of southwestern Angolan Bantu groups are genealogically consistent, suggest that matrilineality strongly enhances both female population sizes and interpopulation mtDNA variation.

genetics↗

bioRxiv2017

Genetic structure and sex-biased gene flow in the history of southern African populations

ObjectivesWe investigated the genetic history of southern African populations with a special focus on their paternal history. We reexamined previous claims that the Y-chromosome haplogroup E1b1b was brought to southern Africa by pastoralists from eastern Africa, and investigated patterns of sex-biased gene flow in southern Africa.\n\nMaterial and MethodsWe analyzed previously published complete mtDNA genome sequences and ~900 kb of NRY sequences from 23 populations from Namibia, Botswana and Zambia, as well as haplogroup frequencies from a large sample of southern African populations and 23 newly genotyped Y-linked STR loci for samples assigned to haplogroup E1b1b.\n\nResultsOur results support an eastern African origin for Y-chromosome haplogroup E1b1b; however, its current distribution in southern Africa is not strongly associated with pastoralism, suggesting a more complex origin for pastoralism in this region. We confirm that the Bantu expansion had a notable genetic impact in southern Africa, and that in this region it was probably a rapid, male-dominated expansion. Furthermore, we find a significant increase in the intensity of sex-biased gene flow from north to south, which may reflect changes in the social dynamics between Khoisan and Bantu groups over time.\n\nConclusionsOur study shows that the population history of southern Africa has been very complex, with different immigrating groups mixing to different degrees with the autochthonous populations. The Bantu expansion led to heavily sex-biased admixture as a result of interactions between Khoisan females and Bantu males, with a geographic gradient which may reflect changes in the social dynamics between Khoisan and Bantu groups over time.

genetics↗