Phosphorylation of the neurogenic transcription factor SOX11 on serine 133 modulates neuronal morphogenesis.

The intellectual disability gene, Sox11, encodes for a critical neurodevelopmental transcription factor with functions in precursor survival, neuronal fate determination, migration and morphogenesis. The mechanisms regulating SOX11's activity remain largely unknown. Mass spectrometric analysis uncovered that SOX11 can be post-translationally modified by phosphorylation. Here, we report that phosphorylatable serines surrounding the high-mobility group box modulate SOX11's transcriptional activity. Through Mass Spectrometry (MS), co-immunoprecipitation assays and in vitro phosphorylation assays followed by MS we verified that protein kinase A (PKA) interacts with SOX11 and phosphorylates it on S133. In vivo replacement of SoxC factors in developing adult-generated hippocampal neurons with SOX11 S133 phospho-mutants indicated that phosphorylation on S133 modulates dendrite development of adult-born dentate granule neurons, while reporter assays suggested that S133 phosphorylation fine-tunes the activation of select target genes. These data provide novel insight into the control of the critical neurodevelopmental regulator SOX11 and imply SOX11 as a mediator of PKA-regulated neuronal development.

Phosphorylation Modulates the Subcellular Localization of SOX11.

SOX11 is a key Transcription Factor (TF) in the regulation of embryonic and adult neurogenesis, whose mutation has recently been linked to an intellectual disability syndrome in humans. SOX11's transient activity during neurogenesis is critical to ensure the precise execution of the neurogenic program. Here, we report that SOX11 displays differential subcellular localizations during the course of neurogenesis. Western-Blot analysis of embryonic mouse brain lysates indicated that SOX11 is post-translationally modified by phosphorylation. Using Mass Spectrometry, we found 10 serine residues in the SOX11 protein that are putatively phosphorylated. Systematic analysis of phospho-mutant SOX11 resulted in the identification of the S30 residue, whose phosphorylation promotes nuclear over cytoplasmic localization of SOX11. Collectively, these findings uncover phosphorylation as a novel layer of regulation of the intellectual disability gene Sox11.

Evaluation of a MetOp ASCAT-Derived Surface Soil Moisture Product in Tundra Environments.

Satellite-derived surface soil moisture data are available for the Arctic, but detailed validation is still lacking. Previous studies have shown low correlations between in situ and modeled data. It is hypothesized that soil temperature variations after soil thaw impact MetOp ASCAT satellite-derived surface soil moisture (SSM) measurements in wet tundra environments, as C band backscatter is sensitive to changes in dielectric properties. We compare in situ measurements of water content within the active layer at four sites across the Arctic in Alaska (Barrow, Sagwon, Toolik) and Siberia (Tiksi), taken in the spring after thawing and in autumn prior to freezing. In addition to the long-term measurement fields, where sensors are installed deeper in the ground, we designed a monitoring setup for measuring moisture very close to the surface in the Lena River Delta, Siberia. The volumetric water content (VWC) and soil temperature sensors were placed in the moss organic layer in order to account for the limited penetration depth of the radar signal. ASCAT SSM variations are generally very small, in line with the low variability of in situ VWC. Short-term changes after complete thawing of the upper organic layer, however, seem to be mostly influenced by soil temperature. Correlations between SSM and in situ VWC are generally very low, or even negative. Mean standard deviation matching results in a comparably high root-mean-square error (on average 11%) for predictions of VWC. Further investigations and measurement networks are needed to clarify factors causing temporal variation of C band backscatter in tundra regions.

A novel approach for the characterization of tundra wetland regions with C-band SAR satellite data.

A circumpolar representative and consistent wetland map is required for a range of applications ranging from upscaling of carbon fluxes and pools to climate modelling and wildlife habitat assessment. Currently available data sets lack sufficient accuracy and/or thematic detail in many regions of the Arctic. Synthetic aperture radar (SAR) data from satellites have already been shown to be suitable for wetland mapping. Envisat Advanced SAR (ASAR) provides global medium-resolution data which are examined with particular focus on spatial wetness patterns in this study. It was found that winter minimum backscatter values as well as their differences to summer minimum values reflect vegetation physiognomy units of certain wetness regimes. Low winter backscatter values are mostly found in areas vegetated by plant communities typically for wet regions in the tundra biome, due to low roughness and low volume scattering caused by the predominant vegetation. Summer to winter difference backscatter values, which in contrast to the winter values depend almost solely on soil moisture content, show expected higher values for wet regions. While the approach using difference values would seem more reasonable in order to delineate wetness patterns considering its direct link to soil moisture, it was found that a classification of winter minimum backscatter values is more applicable in tundra regions due to its better separability into wetness classes. Previous approaches for wetland detection have investigated the impact of liquid water in the soil on backscatter conditions. In this study the absence of liquid water is utilized. Owing to a lack of comparable regional to circumpolar data with respect to thematic detail, a potential wetland map cannot directly be validated; however, one might claim the validity of such a product by comparison with vegetation maps, which hold some information on the wetness status of certain classes. It was shown that the Envisat ASAR-derived classes are related to wetland classes of conventional vegetation maps, indicating its applicability; 30% of the land area north of the treeline was identified as wetland while conventional maps recorded 1-7%.

LRRK2 guides the actin cytoskeleton at growth cones together with ARHGEF7 and Tropomyosin 4.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene represent the most common genetic cause of Parkinson's disease (PD). However, LRRK2 function and molecular mechanisms causing the parkinsonian phenotype remain widely unknown. Most of LRRK2 knockdown and overexpression models strengthen the relevance of LRRK2 in regulating neurite outgrowth. We have recently identified ARHGEF7 as the first guanine nucleotide exchange factor (GEF) of LRRK2. This GEF is influencing neurite outgrowth through regulation of actin polymerization. Here, we examined the expression profile of neuroblastoma cells with reduced LRRK2 and ARHGEF7 levels to identify additional partners of LRRK2 in this process. Tropomyosins (TPMs), and in particular TPM4, were the most interesting candidates next to other actin cytoskeleton regulating transcripts in this dataset. Subsequently, enhanced neurite branching was shown using primary hippocampal neurons of LRRK2 knockdown animals. Furthermore, we observed an enhanced number of growth cones per neuron and a mislocalization and dysregulation of ARHGEF7 and TPM4 in these neuronal compartments. Our results reveal a fascinating connection between the neurite outgrowth phenotype of LRRK2 models and the regulation of actin polymerization directing further investigations of LRRK2-related pathogenesis.