Mechanisms of force generation for vesicle transport processes: identification and characterisation of the Spir actin nucleator - myosin V motor protein complex

The establishment and maintenance of cell polarity constitutes the basis for the morphological and functional diversity of metazoan cells. Intracellular vesicle transport processes mediate the delivery of cell surface receptors, adhesion proteins and other components to the desired locales, in order to define the polarised higher eukaryotic nature of cells. Members of the Rab family of small GTPases thereby act as master regulators for the complex network of trafficking routes, as they specifically attach to intracellular membranes and recruit distinct effector proteins, including motor proteins, in order to facilitate directed transport along microtubule networks and actin tracks. The Rab11 GTPase is critical for exocytic and recycling pathways and has been shown before to recruit the processive actin motor protein myosin V (MyoV) to vesicle surfaces to drive specific cellular functions. Furthermore, there is growing evidence for a coupling of actin assembly by actin nucleation and elongation factors, and myosin motor activity in eukaryotic cells. However, the mechanisms for recruitment of actin nucleators and motor proteins to specific membrane compartments remain unclear. By a set of protein interaction studies, this thesis unravelled a direct physical interaction of the Spir actin nucleators and myosin V motors. The interaction was shown to be mediated by the MyoV globular tail domain (GTD) and a newly identified highly conserved sequence motif (GTBM) in the central Spir linker region and the crystal structure of the Spir-2-GTBM:MyoVa-GTD complex was solved. By means of fluorescence microscopy and FLIM-FRET analysis, the Spir/MyoV interaction was observed in living cells at vesicle membranes as well, proving its biological significance. Further, a regulatory mechanism was revealed in which the Spir-2 protein is able to bind to the back-folded, auto-inhibited MyoV protein and targets it from a cytoplasmic state towards vesicle surfaces. Spir proteins have been shown before to functionally overlap with Rab11 in exocytic and recycling pathways, although a direct Rab11/Spir interaction has never been revealed. The direct interaction of myosin V motors and Spir proteins identified here enables the formation of a tripartite Rab11:MyoV:Spir protein complex at vesicle surfaces in which the MyoV protein acts as a linker between Rab11 and Spir, as was shown by in vitro interaction studies and fluorescence microscopy. The ternary complex architecture would explain how Rab11 vesicles support coordinated F-actin nucleation and myosin force generation for vesicle transport and tethering. Considering the large diversity of MyoV cooperation with Rab family members, the coordinated recruitment of actin nucleators and actin motors to vesicle surfaces could provide a common mechanism to control force generation and motility of vesicles and organelles in different cellular processes

Restoration of Sensitivity in Chemo

Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. Despite multimodal treatments including surgery, chemotherapy and radiotherapy the prognosis remains poor and relapse occurs regularly. The alkylating agent temozolomide (TMZ) has been shown to improve the overall survival in patients with malignant gliomas, especially in tumors with methylated promoter of the O6-methylguanine-DNA-methyltransferase (MGMT) gene. However, intrinsic and acquired resistance towards TMZ makes it crucial to find new therapeutic strategies aimed at improving the prognosis of patients suffering from malignant gliomas. Cold atmospheric plasma is a new auspicious candidate in cancer treatment. In the present study we demonstrate the anti-cancer properties of different dosages of cold atmospheric plasma (CAP) both in TMZ-sensitive and TMZ-resistant cells by proliferation assay, immunoblotting, cell cycle analysis, and clonogenicity assay. Importantly, CAP treatment restored the responsiveness of resistant glioma cells towards TMZ therapy. Concomitant treatment with CAP and TMZ led to inhibition of cell growth and cell cycle arrest, thus CAP might be a promising candidate for combination therapy especially for patients suffering from GBMs showing an unfavorable MGMT status and TMZ resistance

Web 2.0 in der akademischen Praxis: Herausforderungen und strategische Optionen

Das Web 2.0 hat die Kommunikation verändert. Dies gilt zum einen für die Kommunikation im Alltag, für die inzwischen knapp ein Drittel aller Internetnutzer in Deutschland regelmäßig auf Web 2.0-Angebote zurück greifen (Busemann & Gscheidle, 2010). Dies gilt aber auch für die Kommunikation im Hochschulkontext, wo das Web 2.0 von Seiten der Studierenden wie der Hochschulen in den Bereichen Lehre, Forschung und Verwaltung und Dienstleistungen genutzt wird (Hochschulrektorenkonferenz, 2010)

Capacity building for effective social dialogue in the European Union

Aquesta publicació s'elabora a partir de les contribucions de cadascú dels membres nacionals que integren la Network of Eufound Correspondent. Pel cas d'Espanya la contribució ha estat realitzada per l'Oscar MolinaThe aim of this report is to add to the discussion on how Eurofound can contribute to supporting capacity building of social partners for effective social dialogue. The report includes a review by Eurofound aimed at identifying the capacity-building needs and initiatives of social partners in relation to national frameworks for autonomous collective bargaining, involvement in European social dialogue and the European Semester, and the development of membership and services for members. It also includes the results from stakeholder consultations and two exchange seminars held in 2019, along with a set of policy pointers for further discussion

Rab27a co-ordinates actin-dependent transport by controlling organelle-associated motors and track assembly proteins

Abstract: Cell biologists generally consider that microtubules and actin play complementary roles in long- and short-distance transport in animal cells. On the contrary, using melanosomes of melanocytes as a model, we recently discovered that the motor protein myosin-Va works with dynamic actin tracks to drive long-range organelle dispersion in opposition to microtubules. This suggests that in animals, as in yeast and plants, myosin/actin can drive long-range transport. Here, we show that the SPIRE-type actin nucleators (predominantly SPIRE1) are Rab27a effectors that co-operate with formin-1 to generate actin tracks required for myosin-Va-dependent transport in melanocytes. Thus, in addition to melanophilin/myosin-Va, Rab27a can recruit SPIREs to melanosomes, thereby integrating motor and track assembly activity at the organelle membrane. Based on this, we suggest a model in which organelles and force generators (motors and track assemblers) are linked, forming an organelle-based, cell-wide network that allows their collective activity to rapidly disperse the population of organelles long-distance throughout the cytoplasm

Der kriechende Schleim

Wegner C, Welz T. Der kriechende Schleim. Unterricht Biologie. 2015;405(39):41-46

Die Biolampe – Biolumineszenz aquatischer Leuchtbakterien

Wegner C, Welz T. Die Biolampe – Biolumineszenz aquatischer Leuchtbakterien. Unterricht Biologie. 2015;38(401):42-43

Die Maschine des Lebens - Ein Blick auf das Photosystem II

Wegner C, Welz T. Die Maschine des Lebens - Ein Blick auf das Photosystem II. MNU journal. 2020;73(2):117-120

Sanfter Biss, böse Folgen

Wegner C, Welz T. Sanfter Biss, böse Folgen. Praxis der Naturwissenschaften. Biologie in der Schule. 2014;7(63):45-49