Biomedical subjects

M Sachse

Publications and source records attributed to M Sachse.

13 recordsLinked to original sources

PubMed2004

Ubiquitin system-dependent regulation of growth hormone receptor signal transduction.

The growth hormone (GH) receptor is a key regulator of cellular metabolism. Unlike most growth factor receptors, its downregulation is not initiated by its ligand. Like many growth factor receptors, specific molecular mechanisms guarantee that a receptor can signal only once in its lifetime. Three features render the GH receptor unique: (a) an active ubiquitination system is required for both uptake (endocytosis) and degradation in the lysosomes; (b) uptake of the receptor is a continuous process, independent of both GH binding and Jak2 signal transduction; (c) only the cell surface expression of dimerised GH receptors is controlled by the ubiquitin system. This system enables two independent regulatory mechanisms for the endocrinology of the GH/GHR axis: the pulsatile secretion of GH by the pituitary and the GH sensitivity of individual cells of the body by the effects of the ubiquitin system on GH receptor availability.

Animals↗

PubMed2001

Oleaceous laurophyllous leaf fossils and pollen from the European Tertiary.

By using cuticular analysis for the first time laurophyllous leaf remains from the European Tertiary have been reliably identified as belonging to the Oleaceae. Despite ecologically determined variation in cuticular structures, Late Miocene leaf material from northern Italy is assigned to a single species, Oleinites liguricus Sachse n. sp. The associated oleaceous pollen grains support that this species has been a prominent component, at least locally, of a laurophyllous forest community. From extensive comparisons with leaf cuticles and pollen of extant Oleaceae it may be concluded, that the fossil leaves and probably corresponding pollen represent the tribe Oleeae and may originate from a plant closely comparable to extant Chionanthus and Fraxinus. A reinvestigation of some Oligocene laurophyllous leaf remains has uncovered two more oleaceous species in the European Tertiary: Oleinites maii (Buzek et al.) Sachse comb. nov., and Oleinites hallbaueri (Mai) Sachse comb. nov. Considering the high diversity of laurophyllous Oleaceae in modern evergreen and mixed mesophytic forests and the common presence of oleaceous pollen in the fossil record it may be expected that cuticular analysis of laurophyllous leaf fossils will lead to the recognition of an increased number of oleaceous taxa in Tertiary leaf assemblages.

Journal Article↗

PubMed2001

Proteasome inhibitors block a late step in lysosomal transport of selected membrane but not soluble proteins.

The ubiquitin-proteasome pathway acts as a regulator of the endocytosis of selected membrane proteins. Recent evidence suggests that it may also function in the intracellular trafficking of membrane proteins. In this study, several models were used to address the role of the ubiquitin-proteasome pathway in sorting of internalized proteins to the lysosome. We found that lysosomal degradation of ligands, which remain bound to their receptors within the endocytic pathway, is blocked in the presence of specific proteasome inhibitors. In contrast, a ligand that dissociates from its receptor upon endosome acidification is degraded under the same conditions. Quantitative electron microscopy showed that neither the uptake nor the overall distribution of the endocytic marker bovine serum albumin-gold is substantially altered in the presence of a proteasome inhibitor. The data suggest that the ubiquitin-proteasome pathway is involved in an endosomal sorting step of selected membrane proteins to lysosomes, thereby providing a mechanism for regulated degradation.

Animals↗

PubMed2001

The ubiquitin-dependent endocytosis motif is required for efficient incorporation of growth hormone receptor in clathrin-coated pits, but not clathrin-coated lattices.

Endocytosis of the growth hormone receptor (GHR) requires an active ubiquitin-conjugation system. In addition, it depends on a 10 amino acid residues motif in the GHR-cytoplasmic tail, the ubiquitin dependent-endocytosis or UbE-motif. To gain insight into the role of ubiquitination in the early steps of endocytosis, we performed an ultrastructural analysis of GH-uptake in Chinese hamster cells expressing wild-type or mutant GHRs. In wild-type GHR cells, GH was found to be exclusively taken up via clathrin-coated pits. In early endosomes it was efficiently sorted from recycling transferrin and targeted to the degradative pathway. Mutation of all lysine residues of a truncated GHR (GHR-399K-) precludes ubiquitination of the receptor, but internalization of GHR-399K- still depends on an active ubiquitin system. We found that GHR-399K- incorporates GH into clathrin-coated vesicles with the same efficiency as wild-type GHR. By contrast, a mutation in the UbE-motif (GHR-F327A) largely abolished incorporation of GH into clathrin-coated vesicles. Notably, access of GH to clathrin-coated lattices was not affected in GHR-F327A cells. These data corroborate and extend previous data that the UbE-motif but not ubiquitination of the receptor itself recruits GHR into clathrin-coated vesicles. Moreover, they suggest that incorporation of GHR into clathrin-coated lattices is differentially regulated from incorporation into clathrin-coated pits.

Amino Acid Motifs↗

PubMed2000

Growth hormone receptor ubiquitination coincides with recruitment to clathrin-coated membrane domains.

Endocytosis of the growth hormone receptor (GHR) depends on a functional ubiquitin conjugation system. A 10-amino acid residue motif within the GHR cytosolic tail (the ubiquitin-dependent endocytosis motif) is involved in both GHR ubiquitination and endocytosis. As shown previously, ubiquitination of the receptor itself is not required. In this paper ubiquitination of the GHR was used as a tool to address the question of at which stage the ubiquitin conjugation system acts in the process of GHR endocytosis. If potassium depletion was used to interfere with early stages of coated pit formation, both GHR endocytosis and ubiquitination were inhibited. Treatment of cells with methyl-beta-cyclodextrin inhibited endocytosis at the stage of coated vesicle formation. Growth hormone addition to methyl-beta-cyclodextrin-treated cells resulted in an accumulation of ubiquitinated GHR at the cell surface. Using immunoelectron microscopy, the GHR was localized in flattened clathrin-coated membranes. In addition, when clathrin-mediated endocytosis was inhibited in HeLa cells expressing a temperature-sensitive dynamin mutant, ubiquitinated GHR accumulated at the cell surface. Together, these data show that the GHR is ubiquitinated at the plasma membrane, before endocytosis occurs, and indicate that the resident time of the GHR at the cell surface is regulated by the ubiquitin conjugation system together with the endocytic machinery.

Animals↗

PubMed1995

[The content of pepsinogen in the blood plasma of growing fallow deer (Dama dama L.) raised helminth free and under natural conditions in captivity].

Pepsinogen values were determined in helminth free (n = 12) and naturally raised farmed fallow deer (n = 10-12) from birth (June 1992) to 11 (May 1993) and 15 months (September 1993) of age respectively in 4 weekly intervals. At birth the plasma pepsinogen value was 0.708 +/- 0.197 U Tyrosin/l and decreased thereafter until 14 weeks of age to 0.139 +/- 0.061 U Tyrosin/l in both groups. From the 18th week of age the naturally raised fallow deer, infected with gastrointestinal nematodes, had significantly higher pepsinogen values than the helminth free kept animals. Maximum pepsinogen levels in the naturally raised fallow deer were determined in November 1992 (0.813 +/- 0.336 U Tyrosin/l) and in June 1993 (1.050 +/- 0.163 U Tyrosin/l). In helminth free animals no further decrease of plasma pepsinogen values was seen from 14th week of age onwards: it was 0.202 +/- 0.110 U Tyrosin/l. There was no influence of sex on the plasma pepsinogen values in both groups.

Aging↗

PubMed1981