The controlled distribution of sugars between assimilate exporting source tissues and sugar consuming sink tissues is a key element for plant growth and development. Monosaccharide transporters of the SUGAR TRANSPORT PROTEIN (STP) family contribute to the uptake of sugars into sink cells. Here we report on the characterization of STP7, STP8 and STP12, three previously uncharacterized members of this family in Arabidopsis thaliana. Heterologous expression in yeast (Saccharomyces cerevisiae) revealed that STP8 and STP12 catalyze the high-affinity proton-dependent uptake of glucose and also accept galactose and mannose. STP12 additionally transports xylose. STP8 and STP12 are highly expressed in reproductive organs where their protein products might contribute to sugar uptake into the pollen tube and the embryo sac. stp8.1 and stp12.1 T-DNA insertion lines developed normally, which may point towards functional redundancy with other STPs. In contrast to all other STPs, STP7 did not transport hexoses, but was specific for the pentoses L-arabinose and D-xylose. STP7-promoter-reporter gene plants showed an expression of STP7 especially in tissues with high cell-wall turnover, indicating that STP7 might contribute to the uptake and recycling of cell wall sugars. Uptake analyses with radioactive L-arabinose revealed that eleven other STPs are able to transport L-arabinose with high affinity. Hence functional redundancy might explain the missing mutant phenotype of two stp7 T-DNA insertion lines. Together, the data complete the characterization of the STP family and present the STPs as new L-arabinose transporters for potential biotechnological applications.

The tonoplastic inositol transporter INT1 is the only known transport protein in Arabidopsis that facilitates myo-inositol import from the vacuole into the cytoplasm. Impairment of the release of vacuolar inositol by knockout of INT1 results in a severe inhibition of cell elongation in roots as well as in etiolated hypocotyls. Importantly, a more strongly reduced cell elongation was observed when sucrose was supplied in the growth medium, and this sucrose-dependent effect can be complemented by the addition of exogenous myo-inositol. Comparing int1 mutants (defective in transport) with mutants defective in myo-inositol biosynthesis (mips1 mutants) revealed that the sucrose-induced inhibition in cell elongation does not just depend on inositol depletion. Secondary effects as observed for altered availability of inositol in biosynthesis mutants, as disturbed membrane turnover, alterations in PIN protein localization or alterations in inositol-derived signaling molecules could be ruled out to be responsible for impairing the cell elongation in int1 mutants. Although the molecular mechanism remains to be elucidated, our data implicate a crucial role of INT1-transported myo-inositol in regulating cell elongation in a sucrose-dependent manner and underline recent reports of regulatory roles for sucrose and other carbohydrate intermediates as metabolic semaphores.

Prothrombotic hereditary risk factors for cerebral vein thrombosis (CVT) are of clinical interest to better understand the underlying pathophysiology and stratify patients for the risk of recurrence. This study explores prothrombotic risk factors in CVT patients. An initial screening in patients of the outpatient clinic of the Department of Transfusion Medicine and Hemostaseology of the University Hospital Erlangen, Germany, revealed 183 patients with a history of CVT. An initial screening identified a number of common prothrombic risk factors, including Factor V Leiden (rs6025) and Prothrombin G20210A (rs1799963). All patients without relevant findings (58 individuals) were invited to participate in a subsequent genetic analysis of 55 relevant genes using next-generation sequencing (NGS). Three intron variants (ADAMTS13: rs28446901, FN1: rs56380797, rs35343655) were identified to occur with a significantly higher frequency in the CVT patient cohort compared to the general European population. Furthermore, the combined prevalence of at least two of four potentially prothrombic variants (FGA (rs6050), F13A1 (rs5985), ITGB3 (rs5918), and PROCR (rs867186)) was significantly higher in the CVT subjects. The possible impact of the identified variants on CVT is discussed.

The members of a Caucasian family were genetically analyzed on suspicion of hereditary protein S deficiency. A novel mutation, c.1904T>C, associated with severe quantitative protein S deficiency was found. The novel PROS1 mutation was identified by sequencing of the PROS1 gene coding sequence. The identified c.1904T>C point mutation results in p.Phe635Ser amino acid exchange, which is located in the Laminin G-like 2 domain of protein S. Computational analysis indicates that this amino acid exchange affects the correct folding of the protein S antigen. Furthermore, this mutation is located in a region of the Laminin G-like 2 domain where changes in the amino acid sequence often result in decreased secretion. We postulate that the novel p.Phe635Ser mutation might lead to an incorrect folding, and thus, to a strongly impaired secretion of this protein S variant. We named this novel variant protein