Project P12 | Achim Paululat
Plasticity and adaptation of the endocytic membrane compartment in nephrocyte differentiation
We focus on the biogenesis and plasticity of labyrinth channels at the plasma membrane of Drosophila kidney-like nephrocytes and their link to the endolysosomal system during growth and aging.
Prof. Dr. Achim Paululat
School of Biology/Chemistry
Research Group Zoology
Unlike vertebrates, insects harbour a mixture of blood and body fluids called the haemolymph, which circulates directly within the body cavity of the animal. Haemolymph clearance, detoxification, waste storage, water balance, and osmoregulation in Drosophila, as in all insects, are carried out by two physically separate organ systems, the Malpighian tubules (renal tubes), and by about 60-80 single individual cells, the nephrocytes. They perform similar tasks in insects as the mammalian kidney with its podocytes (Beyenbach et al., 2020).
Nephrocytes are primarily acting as scavenger cells that adapt in several ways to their dedicated function: (i) they grow by polyploidism into cells of more than 100 µm diameter, (ii) their endocytic and degradation pathways are highly upregulated, (iii) their plasma membrane invaginations form a labyrinth channel system as an endocytic active zone, and (iv) they harbour a slit diaphragms (SD) as filtration barrier at the entries to the channels, which are intracellular adherens junctions.
We will focus here on the functional plasticity of the labyrinth channel and the associated endocytic membrane system that allow nephrocytes to functionally adapt to ageing, toxic stress, disease and variable demands.
Klinke, N., Meyer, H., Ratnavadivel, S., Reinhardt, M., Heinisch, J.J., Malmendal, A., Milting, H., Paululat, A. (2022) A Drosophila melanogaster model for TMEM43 related Arrhythmogenic right ventricular cardiomyopathy type 5. Cell Mol Life Sci 79: 444.
Schiemann, R., Buhr, A., Cordes, E., Walter, S., Heinisch, J.J., Ferrero, P., Milting, H., Paululat, A., Meyer, H. (2022) Neprilysins regulate muscle contraction and heart function via cleavage of SERCA-inhibitory micropeptides. Nature Commun 13: 4420.
Psathaki, O.-E. Paululat, A. (2022) Preparation of Drosophila tissues and organs for transmission electron microscopy. Methods Mol Biol 2540: 361-385.
Paradis, M., Kucharowski, N., Edarwds Farat, G., Palacios, S.J.M., Meyer, C., Stümpes, B., Jamitzky, I., Kalinoswski, J., Thiele, C., Bauer, R., Paululat, A., Sellin, J., Bülow, M. (2022) The ER protein Creld regulates ER-mitochondria contact dynamics and respiratory complex activity. Sci Adv 8: eabo0155.
Breitsprecher, L.F., Tiburcy, F., Furuse, M., Izumi, Y., Meyer, H., Jonusaite, S., Rodan, A.R., Paululat, A. (2020). The septate junction protein Tetraspanin 2A is critical to the structure and function of Malpighian tubules in Drosophila melanogaster. Am J Physiol Cell Physiol 318, C1107-C1122.
Dehnen, L., Janz, M., Kumar Vermar, J., Psathaki, O.E., Langemeyer, L., Fröhlich, F., Heinisch, J.J., Meyer, H., Ungermann, C. Paululat, A. (2020) A trimeric metazoan Rab7 GEF complex is crucial for endocytosis and scavenger function. J Cell Sci 133, jcs.247080.
Wilmes, A.C., Klinke, N., Rotstein, B., Meyer, H., Paululat, A. (2018) Biosynthesis and assembly of the Collagen IV-like protein Pericardin in Drosophila melanogaster. Biol Open 7, bio030361.
Rotstein, B., Post, Y., Reinhardt, M., Lammers, K., Buhr, A., Heinisch, J.J., Meyer, H. Paululat, A. (2018) Distinct domains present in the matricellular protein protein Lonely heart are crucial for cardiac extracellular matrix formation and heart function in Drosophila melanogaster. J Biol Chem 293, 7864-7879.
Drechsler, M., Meyer, H., Wilmes, A.C. Paululat, A. (2018) APC/CFzr regulates cardiac and myoblast cell numbers and plays a crucial role during myoblast fusion. J Cell Sci 131, pii: jcs209155.
Psathaki, E.O., Dehnen, L., Hartley, PS. Paululat, A. (2018) Drosophila pericardial nephrocyte ultrastructure changes during ageing. Mech Ageing Dev 173: 9-20.