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The adhesion G-protein-coupled receptor GPR133 (ADGRD1) supports growth of the brain malignancy glioblastoma. How the extracellular interactome of GPR133 in glioblastoma modulates signaling remains unknown. Here, we use affinity proteomics to identify the transmembrane protein PTK7 as an extracellular binding partner of GPR133 in glioblastoma. PTK7 binds the autoproteolytically generated N-terminal fragment of GPR133 and its expression in trans increases GPR133 signaling. This effect requires the intramolecular cleavage of GPR133 and PTK7's anchoring in the plasma membrane. PTK7's allosteric action on GPR133 signaling is additive with but topographically distinct from orthosteric activation by soluble peptide mimicking the endogenous tethered Stachel agonist. GPR133 and PTK7 are expressed in adjacent cells in glioblastoma, where their knockdown phenocopies each other. We propose that this ligand-receptor interaction is relevant to the pathogenesis of glioblastoma and possibly other physiological processes in healthy tissues. [Display omitted] • PTK7 is a GPR133-binding protein in glioblastoma • PTK7-GPR133 binding takes place between their extracellular N-terminal domains • PTK7 binding in trans increases GPR133 signaling • Knockdown of either GPR133 or PTK7 impairs glioblastoma tumorsphere formation Frenster et al. identify PTK7 as a GPR133-binding protein in glioblastoma. Interaction of their extracellular domains in trans allosterically increases GPR133 signaling. This effect requires GPR133's autoproteolytic cleavage and PTK7's plasma membrane anchorage. PTK7 and GPR133 are expressed in adjacent cells in glioblastoma, where knockdown of either impairs tumor growth. [ABSTRACT FROM AUTHOR]

Seven new isolates of the heterokont algal class Synchromophyceae are described from coastal habitats of the Atlantic Ocean, including the Caribbean and Mediterranean Seas. All of the new isolates contain chloroplast complexes, a key feature of this group of algae. Morphology, pigments and DNA sequences support a monophyletic grouping of the Synchromophyceae to the exclusion of other Ochrophyta (primarily photosynthetic stramenopiles). Within the Synchromophyceae, two phylogenetic clades based on rbcL and 18S rDNA data were discovered, which differ in cell size and also the number of plastid complexes per cell. Two isolates form a clade with the type species Synchroma grande, while all other isolates form a separate clade, including the newly described species S. pusillum. Further species delineation of the isolates is difficult due to the highly similar morphology and life cycle strategy. Phylogenetic relationships with other genera of the Ochrophyta, such as Leukarachnion and Chlamydomyxa, are apparent and shed light on a heterogeneous branch of heterokont evolution. [ABSTRACT FROM AUTHOR]

Chromist algae including the Heterokontophyta are supposed to have evolved monophyletically by secondary endosymbiosis from a eukaryotic host cell that engulfed a eukaryotic red alga. The red algal endosymbiont was then reduced to a secondary plastid surrounded by four enveloping membranes. On the basis of the amoeboid marine alga Synchroma grande gen. et spec. nov., the Synchromophyceae are described here as a new class of Heterokontophyta. Their taxonomic position is characterized by 18S rRNA and rbcL gene phylogenies, morphology, and pigment composition. The so far unique feature of the Synchromophyceae is the occurrence of conspicuous chloroplast complexes representing multiplastidic red secondary endosymbionts. In these remarkable secondary endosymbionts, several primary chloroplasts are aggregated in a common periplastidial compartment and are collectively enveloped by an additional outer membrane pair. The discovery of this novel plastid morphology is highly relevant for research on algal evolution and is discussed in terms of the postulated monophyletic origin of Chromista. [Copyright &y& Elsevier]

EXOSC3-related autosomal recessive neurodevelopmental disorders are rare entities with variable clinical course and prognosis. They are characterized by hypoplasia of cerebellar structures and pons, degeneration of the anterior horn cells and motor as well as neurocognitive impairment. Phenotypic expression is variable with an overall poor outcome. Current research suggests clear genotype-phenotype correlations among EXOSC3 -pathogenic-variants carriers. Homozygosity for the EXOSC3 variant c.395A > C, p.(Asp132Ala) is proposed to lead to a rather mild phenotype compared to compound-heterozygous EXOSC3 -pathogenic-variants carriers with lethal neurological disease in very early childhood. In this study, we report two siblings (21- and 8-year-old) affected by PCH1B with an unusual presentation. We identified compound heterozygosity for the well-established EXOSC3 variant c.395A > C, p.(Asp132Ala) and the novel variant c.572G > A, p.(Gly191Asp), expanding the genetic spectrum. Phenotypic presentation of the siblings was strikingly different from that of literature reports with a surprisingly mild disease manifestation and an unexpected intrafamilial variability. This study demonstrates the extensive clinical heterogeneity and the broad phenotypic spectrum associated with EXOSC3 -associated disorders. Enlargement of sample sizes and reports of novel cases will be essential for the delineation of associated phenotypes. [ABSTRACT FROM AUTHOR]

Accurate classification of melanocytic proliferations has important implications for prognostic prediction, treatment and follow-up. Although most melanocytic proliferations can be accurately classified using clinical and pathological criteria, classification (specifically distinction between nevus and melanoma) can be challenging in a subset of cases, including those with spitzoid morphology. Genetic studies have shown that mutation profiles differ between primary melanoma subtypes and Spitz nevi. These differences may aid in distinguishing benign from malignant in some melanocytic tumours. Here, we present a selection of melanocytic proliferations with equivocal histopathological criteria, wherein genetic analysis was requested to help guide classification. In two of four cases, the genetic results offered valuable insights, allowing a definitive diagnosis, indicating the diagnostic value of mutation profiling in a real-world routine clinical setting. Although histopathological assessment remains decisive in melanocytic proliferation classification, we recommend including genetic profiling in cases of borderline or atypical lesion to support accurate classification. • Mutation analysis can be a diagnostic aid in determining the dignity in some spitzoid tumours. • Where no gene mutations are identified, translocation analysis should be considered. • Molecular analysis aids in identifying malignant tumours to be treated as melanoma. [ABSTRACT FROM AUTHOR]