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3. Nanodomains for Excitability


targets processes such as signalling by Ca2+ channels and the ensuing Ca2+-triggered membrane fusion – the hallmarks of excitable cells. It focuses especially on voltage-gated Ca2+ channels (CaV) and ryanodine receptors (RyR, Ca2+-release channels of the endoplasmic reticulum) in sensory hair cells and atrial cardiomyocytes. We use converging bottom-up and top-down approaches to comparatively study the assembly, function and dysfunction of CaV1.3 and RyR2 and develop virus-mediated gene replacement as a therapeutic strategy targeting the presynaptic CaV1.3 channel complex. Another focus are Ferlins, multi-C2-domain proteins, that are essential for synaptic vesicle exocytosis at the presynaptic active zones of hair cells (otoferlin) and for plasma membrane resealing and T-tubule remodelling in cardiomyocytes (dysferlin). Genetic defects cause deafness (otoferlin) and cardiomyopathy (dysferlin). We will elucidate the structure and function of the molecular machineries of membrane fusion in hair cells and cardiomyocytes.
Research Alliance 3.1: Assembly and Function of ion Channel Clusters
Research Alliance 3.2: Calcium triggered Membrane Fusion


Research Alliance 3.1: Assembly and Function of Ion Channel Clusters

investigates how cytoplasmic ribosomes select the appropriate targeting machinery for membrane protein precursors.

How does proper targeting ensure the maintenance of cardiac Ca2+-release units or of the neuronal membrane fusion machinery?

The membrane proteins under investigation will allow us to determine the contribution of targeting deficits to the pathogenesis of inherited neurocardiac disorders.

Moderator

Prof. Dr. Claudia Steinem
Institute of Organic and Biomolecular Chemistry
University of Göttingen
Tammannstr. 2
37077 Göttingen
csteine@gwdg.de


Research Groups


Research Alliance 3.2: Calcium triggered Membrane Fusion

The process of Ca2+-triggered membrane fusion is of fundamental importance in excitable cells. Neurons and neurosensory cells, such as the hair cells of the auditory pathway, rely on the Ca2+-triggered fusion of neurotransmitter-filled synaptic vesicles (SV) with the plasma membrane for synaptic signalling and information processing. Cardiomyocytes also require Ca2+-triggered vesicle fusion to release atrial natriuretic factor (ANF) and other peptide hormones from atrial cardiomyocytes, for trafficking of glucose transporters to the plasma membrane, and for resealing plasma membrane defects that arise from membrane stress during contraction and stretching.

These different fusion mechanisms likely share fundamental similarities, but their commonalities and differences are poorly known and therefore of major interest to this Research Alliance.

In sensory cells and in cardiomyocytes, the function of synaptotagmin is thought to be taken over by other C2-domain proteins, the ferlin family members (otoferlin in hair cells, dysferlin in myocytes). Otoferlin and dysferlin are major research targets as they play a role in sensorineural hearing impairment and cardiomyopathy. We focus on the elucidation of the structure and function of ferlins in vitro, we want to understand the cellular organization and function of ferlins, in comparison to synaptotagmin and eventually work towards gene replacement and gene correction by genome editing for ferlinopathies.

Moderator

Prof. Dr. Tobias Moser
Institute of Auditory Neuroscience
University Medical Center Göttingen
Robert-Koch-Str. 40
37075 Göttingen
tmoser@gwdg.de


Research Groups

Open Positions

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