Pharmacopsychiatry 2009; 42 - A152
DOI: 10.1055/s-0029-1240224

The novel stress inducible gene MPIP101 modulates neurite formation via changes in Actin dynamics

JP Schülke 1, C Liebl 1, M Stiess 2, N Zimmermann 1, MV Schmidt 1, C Avrabos 1, GM Wochnik 1, D Trümbach 3, F Bradke 2, M Eder 1, MB Müller 1, T Rein 1
  • 1Max Planck Institute of Psychiatry, Munich, Germany
  • 2Max Planck Institute of Neurobiology, Martinsried, Germany
  • 3Helmholtz Centre, Neuherberg, Germany

In a collaborative study (see poster by Liebl et al.) we have identified MPIP101 as a novel transcript that is stress regulated via glucocorticoids. This gene encodes for a small hypothetical protein of unknown function. In vivo overexpression revealed that the protein influences behaviour and electrophysiological properties in the hippocampus. To elucidate the molecular function of this protein we performed immunoprecipitation experiments and identified Prdx1, PRMT5 and beta-Actin as interacting partners of MPIP101. Immunofluorescence experiments in cells revealed a clear colocalization with F-Actin structures and an increase of these structures upon overexpression of MPIP101. Furthermore, recombinant MPIP101 binds to F-Actin in vitro and stabilizes filaments formed in the presence of MPIP101. Fluorescence visualization of the F-Actin filaments revealed that MPIP101 induces bundling of filaments. In cells, MPIP101 also influences Actin dependent processes, evidenced by a reduced neurite outgrowth in both Neuro2a cells and primary neurons. Endogenous MPIP101, mostly expressed in the CNS, colocalizes with F-Actin and localizes to synapses and, notably, dendritic spines. We propose that stress related behavioural changes may be partly regulated by altered protein levels of MPIP101. This may be reflected by changes in the electrophysiological properties, mediated by modulating Actin dynamics in interneuronal connections.