Biophysical characterization and analysis of the cellular function of the neuronal Calciumsensor proteins Caldendrin and Calneurons

• Applicant: Dr. Michael R. Kreutz
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2010 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 167919966

The transduction of Ca2+-signals in the brain plays a pivotal role in such diverse and fundamental processes as neurodegeneration, synaptic plasticity and neuronal development [1, 2], This broad range of different Ca2+-triggered phenomena is reflected by the existence of a multitude of different Ca2+-binding proteins (CaBPs) from which numerous belong to the EF-hand super-family [2]. Neuronal calcium sensor (NCS) proteins are members ofthe EFhand super-family that play multiple and divergent roles in neuronal signaling. They closely resemble the structure of their common ancestor Calmodulin with four EF-hand Ca2+-binding motifs. Despite their relatively high degree of similarity NCS proteins are thought to serve highly specialized functions in neurons. It is generally believed that the specificity with respect to their target interactions is brought about by either a restricted subcellular localization, differences in Ca2+-binding affinities or modifications of their EF-hand structure that might provide a unique interface for protein interactions. In this application we want to analyze the molecular dynamics and cellular function of the neuronal Ca2+-binding proteins Caldendrin and Calneurons. We will prove the hypothesis that Caldendrin is a synaptic Ca2+- and Zn2+ sensor that rapidly changes the conformation of its synaptic binding partner PSD95, a mechanism that could contribute to short-term potentiation at the synapse. In addition we want to investigate the mechanisms by which Calneurons are targeted to the trans-Golgi network and regulate stimulus-dependent dynamics in trans-Golgi network to plasma membrane trafficking.

• DFG Programme: Research Grants
• International Connection: India
• Partner Organisation: Department of Science and Technology (DST)
• Participating Person: Yogendra Sharma, Ph.D.