Neural plasticity and communication
Prof. Dr. rer. nat. D. C. Dieterich
Upon brain development a highly efficient communication network forms between neurons and glia cells via the establishment of numerous synapses. This process, also known as synaptogenesis, as well as long lasting forms of synaptic plasticity are characterized by dynamic changes of the neuronal proteome. Besides the synthesis of new proteins and their correct placement within the cell, posttranslational modifications and the directed degradation of distinct proteins play vital roles for synaptic and cellular function. Interestingly, neurons are capable of synthesizing proteins not only in the soma but also locally in distal parts of their dendrites. This local protein synthesis allows synapses to respond dynamically to changes in their activity pattern. To date numerous neuronal, especially synaptic proteins, have been identified, but much less is known about the dynamic changes of these proteomes during synaptogenesis and synaptic plasticity. Especially the specificity and dynamics of the astroglial proteome is not well explored, perhaps because their role during neuronal development and plasticity has been underestimated for a long time. However, recent findings suggest an equal partnership between astrocytes and neurons both during development and after maturation. Therefore, the investigation of astroglial proteome dynamics is one of our major aims.
Aside from de novo protein synthesis, posttranslational modifications such as phosphorylation and glycosylation are invaluable means by which cells can adjust to changes in their activity pattern. Fucosylation, for instance, has been implicated in several synaptic plasticity and learning-associated processes. However, the identity and specificity of key fucosylated proteins for individual plasticity models, i.e. signature proteins, remains elusive. Therefore, one of our research focuses on the identification and function of fucosylated glycans.
For our investigations we employ a suite of recently developed tools using small chemical reporters to metabolically label newly synthesized proteins, glycosylated proteins, or lipids. The core of all these metabolic labeling techniques capitalizes on the manifold potential of small bioorthogonal chemo-selective groups. These groups deliver unique chemical functionality to their target molecules, which can subsequently be tagged with exogenously delivered probes for detection or isolation in a highly selective manner.
To specifically label newly synthesized proteins BONCAT (bioorthogonal non-canonical amino acid tagging) and FUNCAT (fluorescent non-canonical amino acid tagging) were developed. These complementary techniques enable one to identify and visualize the subpopulation of newly synthesized protein using bioorthogonal non-canonical amino acids by utilizing the cell’s own translation machinery in a highly specific fashion. To label glycosylated proteins or lipids, appropriate artificial azide-bearing monosaccarides or fatty acids, respectively, can be used.