This Week in PNAS
EVOLUTION
Silk genes shed light on spider evolution
Jessica Garb and Cheryl Hayashi identified and characterized gene variants encoding silken egg case fibers in spiders, and their findings provide insight into spider evolution and could help researchers develop applications with spider silk. Garb and Hayashi found variants of the gene TuSp1 in 12 members of the broad taxonomic group of orb-weaving spiders Orbicularia. TuSp1 protein is used by female spiders to make egg case silk. The authors found that TuSp1 protein consists of a few arrayed repeat units ≈200 aa in length. These repeats in different species contained strong similarities, even among taxa that diverged 125 million years ago. Analyses of repeats within and across species revealed the influence of concerted evolution, where mutations are spread from one repeat to the next, resulting in intragenic homogenization. The TuSp1 repeats of the Deinopoidea superfamily of Orbicularia contained insertions of coding minisatellite-like sequences, an apparent result of DNA replication slippage and nonreciprocal recombination. Phylogenetic comparisons with 25 other spider silk genes showed that the 12 TuSp1 variants are divergent members of a spider gene family and are the result of an ancient gene duplication. — P.D.
Spider silken egg case.
“Modular evolution of egg case silk genes across orb-weaving spider superfamilies” by Jessica E. Garb and Cheryl Y. Hayashi (see pages 11379–11384)
IMMUNOLOGY
Mast cell progenitors identified
Ching-Cheng Chen et al. have isolated mast cell progenitors (MCPs) from adult mice. Previous research has shown that mast cells are derived from hematopoietic stem cells (HSCs); however, in adult hematopoiesis, finding a committed MCP has proven difficult. Chen et al. characterized candidate progenitors purified from adult mouse bone marrow cells. After fractionating based on β7 integrin (β7), expressed on bone marrow-derived cultured mast cells, and CD27, a marker for HSCs and progenitors, the authors found that the majority of the mast cell-generating activity resided in the β7+CD27– fraction. Further sorting based on expression of T1/ST2, part of the IL-1 receptor family, combined with culturing in a cytokine cocktail, led to identification of β7+T1/ST2+ cells as MCPs. These cells generated pure populations of mast cells after as few as 5 days in culture. Chen et al. transplanted the MCPs into mast cell-deficient mice and found mature, donor-derived mast cells in only the MCP-transplanted animals and not in controls. By examining the mast cell-generating potential of various progenitor populations, adult MCPs were shown to derive directly from multipotent progenitors and not from common myeloid progenitors or granulocyte/macrophage progenitors, as had been previously proposed. — F.A.
Progenitors developed into mast cells.
“Identification of mast cell progenitors in adult mice” by Ching-Cheng Chen, Michele A. Grimbaldeston, Mindy Tsai, Irving L. Weissman, and Stephen J. Galli (see pages 11408–11413)
MEDICAL SCIENCES
Deep-organ malaria parasite not associated with cerebral complications
Blandine Franke-Fayard et al. demonstrate that cerebral malaria pathology can occur in the absence of parasite sequestration. The sequestration of the malaria parasite Plasmodium falciparum in the microvasculature of deep organs (e.g., brain, liver, and lung) has been thought to underlie the severe complications of infection, such as cerebral malaria. Although parasite-encoded proteins on the surface of infected red blood cells are thought to act as anchors to endothelial cells within the brain, the relationship of sequestration with cerebral complications has never been firmly established. Franke-Fayard et al. visualized the interactions between infected red blood cells and the putative host receptor, CD36. By tagging rodent Plasmodium berghei parasites with luciferase, sequestration in expected organs, such as lung and spleen, was observed, but adipose tissue was also a major sequestration site. CD36 was shown to be the major receptor for P. berghei sequestration. Mice lacking CD36, the presumed host receptor for infected red blood cells, showed no parasite sequestration, but still developed cerebral malaria. With an eye on the development of novel antimalarial therapies, these results help pinpoint relevant interactions between parasite-infected cells and host cells. — M.M.
“Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration” by Blandine Franke-Fayard, Chris J. Janse, Margarida Cunha-Rodrigues, Jai Ramesar, Philippe Büscher, Ivo Que, Clemens Löwik, Peter J. Voshol, Marion den Boer, Sjoerd G. van Duinen, Maria Febbraio, Maria M. Mota, and Andrew P. Waters (see pages 11468–11473)
Distribution of malaria parasites in live rodents.
NEUROSCIENCE
TRPM7 allele may increase risk of Guamanian ALS and parkinsonism dementia
Meredith Hermosura et al. report that a mutation in the transient receptor potential melastatin 7 (TRPM7) ion channel may contribute to Guamanian amyotrophic lateral sclerosis (ALS-G) and parkinsonism dementia (PD-G). These conditions are related neurodegenerative disorders found in high incidence on Guam and other western Pacific islands. TRPM7 is involved in homeostatic regulation of intracellular calcium (Ca2+) and magnesium (Mg2+), elements whose deficiency has been epidemiologically linked to ALS-G and PD-G. Hermosura et al. show that the missense mutation T1482I (affecting threonine 1482, or Thr-1482) results in a functional TRPM7 channel that displays similar kinase activity to wild type but has increased sensitivity to inhibition by intracellular Mg2+. Mg2+ inhibition correlates with phosphorylation of Thr-1482, though the exact mechanism is not known. The authors propose that cells expressing the TRPM7 variant will have a higher likelihood of becoming deficient in Ca2+ and Mg2+, and therefore the T1482I genotype may confer susceptibility to ALS-G and PD-G in regions that have low concentrations of these ions, such as some environments in the western Pacific. — N.Z.
Cells overexpressing wild-type and T1482I TRPM7 channels, showing similar channel trafficking and localization.
“A TRPM7 variant shows altered sensitivity to magnesium that may contribute to the pathogenesis of two Guamanian neurodegenerative disorders” by Meredith C. Hermosura, Hannah Nayakanti, Maxim V. Dorovkov, Fernanda R. Calderon, Alexey G. Ryazanov, David S. Haymer, and Ralph M. Garruto (see pages 11510–11515)
