Institute of Biochemistry

Michael M. Kessels lab - Research Group Cell Biology of the Cytoskeleton

(Research Institute of the FSU Jena / Institute for Biochemistry I)

The actin cytoskeleton is composed of a plethora of single molecules, which are organized in filaments and superstructures thereof. The actin cytoskeleton is continuously being remodeled and this dynamic remodeling is essential for eukaryotic cells. It allows cells to respond to intracellular and extracellular stimuli and is indispensable for cell division, establishment and changes in cellular morphology and cell adhesion-processes. Such processes for example play an important role during embryonic development, wound healing as well as the formation of neuronal networks.

As cytoskeletal forces are a major source for defining, keeping and changing the morphology and subcellular organization of cells and these processes are crucial for the formation of the complex tissues and organs of multicellular organisms, we study the molecular mechanisms and the cellular functions of components of the actin cytoskeleton and hereby focus on the machines that catalyze the critical step of actin filament formation, i.e. the assembly of an actin nucleus. These components are called actin nucleators.

The required morphological and functional organization of cellular membrane structures and compartments as well as of membrane transport processes depends on a coordinated work of a variety of molecules that are part of the membrane-associated, cortical actin cytoskeleton. One main research focus therefore is to identify and characterize molecular players at the functional interface between membrane dynamics and the cortical actin cytoskeleton. We have discovered novel proteins that are able to mediate such interconnections, e.g. the actin-binding protein Abp1.

 

Research Projects

Functional analyses of Abp1 - Genetic, cell biological and biochemical examinations in the model organism Drosophila melanogaster show that the correct development of sensory organs, such as eyes and bristles, as well as the proper generation of neuromuscular synapses require actin filament formation mediated by the F-actin binding protein Abp1 at the cell cortex. The project therefore examines the abilities of Abp1 to bind to actin filament, to membranes and to activate the Arp2/3 complex in vitro as well as in the complete organism (Pinyol et al. 2007, Plos ONE;  Koch et al. 2012, J. Cell Sci.).

Fig-1-MK 2013

Figure 1. Cells of the central nervous system are characterized by a particularly high degree of specialization and differentiation not only functionally but also structurally, as visualized for cultured hippocampal neurons (right) as well as for Drosophila embryos (left).

 

The novel actin nucleator Cordon-Bleu (Cobl) and its role in neuronal morphogenesis and network formation - In the course of this project we have identified a novel actin nucleator (Ahuja et al. 2007, Cell). Ongoing studies aim at understanding its actin nucleation mechansims, its functions and its importance in different cellular functions. Therefore, we investigate the mechansims Cobl uses by mutational and structural examinations, analyze the protein interactions of Cobl with a variety of methods in vitro as well as in living cells and furthermore investigate its cell biological functions in neuromorphogenesis and in the proper formation of neuronal structures (Haag et al. 2012, J. Neurosci.; Schüler et al. 2013, J. Cell Sci.).

The role of cytoskeletal and cytomatrix components in the structural and functional organization of neurons - Nerve cell communication requires specialy subcellular compartments and structures, which need to be organized on the molecular level. The project examines the molecular basis of Abp1 functions in the formation and the plasticity of synaptic cell-cell contacts (Häckel et al. 2008, J. Neurosci.) and in the neuromorphogenesis processes underlying the formation of neuronal networks. In recent studies, we were able to reveal that F-actin-anchored Cobl/Abp1 complexes seem crucial for neuromorphogenesis processes, particularly for the postnatal arborization of Purkinje cells representing the source for all motor coordination in the cerebellar cortex (Haag et al. 2012, J. Neurosci.). Our work therefore significantly contributes to the understanding of the importance of cytoskeletal reorganizations for the establishment of specialized morphological structures that are for example indispensable for the plasticity of neurons and for the organization of neuronal networks.

Fig-2-MK2013

Figure 2. The actin nucleator Cobl is crucial for the development of Purkinje cell architecture in the cerebellum For details see publication and cover illustration in Journal of Neuroscience (Haag et al. 2012, J. Neurosci.).

 

Further Research projects at the institute see

Institute for Biochemistry I - Britta Qualmann
Research Group Proteomics - Heidrun Rhode lab