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Project A03: Neuronal actin dynamics shaping resilience: the role of the novel actin-interacting protein ‘downregulated in renal cancer’ (DRR1)

Principal Investigators

Prof. Dr. Marianne Müller

Professor

Group Leader at LIR

Prof. Dr. Amparo Acker-Palmer

Professor

Project Team

Our Research

A03 investigates the function of the protein DRR1, whose stressor-induced DRR1 up-regulation is a candidate active neural resilience mechanism. A01 proposes that DRR1 regulates the actin-dependent insertion of AMPA receptors at the synapse. Hippocampal AMPA receptor function in turn affects resilience, suggesting a link from stressor-induced changes in the transcriptome via regulation of neural excitability in the hippocampus to resilience. The authors will further apply hypothesis-free approaches serving to discover further molecular candidates, including RNA sequencing of DRR1 overexpressing mice after stress exposure.

Publications

Harde E, Nicholson L, Furones Cuadrado B, Bissen D, Wigge S, Urban S, Segarra M, Ruiz de Almodóvar C, Acker-Palmer A (2019) EphrinB2 regulates VEGFR2 during dendritogenesis and hippocampal circuitry development. eLife 8. pii: e49819. doi: 10.7554/eLife.49819.

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Jene T, Gassen NC, Opitz V, Endres K, Müller MB*, van der Kooij MA* (2018) Temporal profiling of an acute stressinduced behavioral phenotype in mice and the role of hippocampal DRR1. Psychoneuroendocrinology 91:149–158. *equal contribution

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Masana M, Westerholz S, Kretzschmar A, Treccani G, Liebl C, Santarelli S, Dournes C, Popoli M, Schmidt MV, Rein T, Müller MB (2018) Expression and glucocorticoid-dependent regulation of the stress-inducible protein DRR1 in the mouse adult brain. Brain Struct Funct 223(9):4039–4052.

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van der Kooij MA*, Jene T*, Treccani G, Miederer I, Hasch A, Voelxen N, Walenta S, Müller MB (2018) Chronic social stress-induced hyperglycemia in mice couples individual stress susceptibility to impaired spatial memory. Proc Natl Acad Sci USA 115(43):E10187–E10196. *equal contribution

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Kalisch R, Baker DG, Basten U, Boks MP, Bonanno GA, Brummelman E, Chmitorz A, Fernàndez G, Fiebach CJ, Galatzer-Levy I, Geuze E, Groppa S, Helmreich I, Hendler T, Hermans EJ, Jovanovic T, Kubiak T, Lieb K, Lutz B, Müller MB, Murray RJ, Nievergelt CM, Reif A, Roelofs K, Rutten BPF, Sander D, Schick A, Tüscher O, Van Diest I, van Harmelen A-L, Veer IM, Vermetten E, Vinkers CH, Wager TD, Walter H, Wessa M, Wibral M, Kleim B (2017) The resilience framework as a strategy to combat stress-related disorders. Nat Hum Behav 1:784-90.

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Pfennig S, Foss F, Bissen D, Harde E, Treeck JC, Segarra M, Acker-Palmer A (2017) GRIP1 binds to ApoER2 and EphrinB2 to induce activity-dependent AMPA receptor insertion at the synapse. Cell Rep 21(1):84–96.

>> Link to PubMed