The actin nucleator Cordon-Bleu (Cobl) - elucidation of regulatory mechanisms and cellular function - II

• Applicant: Privatdozent Dr. Michael Manfred Kessels
• Subject Area: Cell Biology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2011 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 192290875

Actin filament polymerization is essential for processes as diverse as cell morphology control, the formation of multicellular networks, cell migration and membrane trafficking processes. Indispensable is thereby a tight spatial and temporal control of actin filament nucleation. With the multiple WH2 domain-containing protein Cobl, we have identified a novel and very powerful actin nucleator. Our studies have thereby unraveled that Cobl plays an important role in proper formation of neuronal cell morphology - a prerequisite for the formation of functional neuronal networks. Analyses on the tissue and organism level now aim at revealing the structural and functional pathophysiological consequences of an impaired neuromorphogenesis upon Cobl deficiency. The successful establishment of Cobl-deficient organisms has furthermore already allowed first insights into the role of this new actin nucleator in cellular development, differentiation and function in the intact organism. These studies show among other phenotypes strikingly that different types of ciliary structures rely on the function of the actin nucleator Cobl. Ciliopathies, genetically inherited defects of these sensory cell surface structures, span a wide range of pleiotropic clinical phenotypes including frequently neurodevelopmental defects. Subsequent investigations will address the underlying mechanisms and shall disclose the exact role of Cobl-mediated cortical actin dynamics in the establishment of ciliary structures and reveal the pathophysiological consequences of a Cobl-deficiency on ciliogenesis and neuronal development.The analysis of the consequences of a loss of Cobl at the cellular, tissue and organism level is expected to significantly expand our molecular understanding of the functions of the cortical actin cytoskeleton - functions that are indispensable for live of all higher eukaryots.

• DFG Programme: Research Grants