Brain malformations and seizures by impaired chaperonin function of TRiC.

Malformations of the brain are common and vary in severity, from negligible to potentially fatal. Their causes have not been fully elucidated. Here, we report pathogenic variants in the core protein-folding machinery TRiC/CCT in individuals with brain malformations, intellectual disability, and seizures.

Phorbol-12-myristate-13-acetate is a potent enhancer of B cells with a granzyme B regulatory phenotype.

Introduction: The infusion of -generated regulatory B cells may represent a promising novel therapeutic approach for a variety of autoimmune and hyperinflammatory conditions including graft-versus-host disease.

Methods: Previously, we developed a protocol for the generation of a novel population of regulatory B cells, which are characterized by secretion of enzymatically active granzyme B (). This protocol uses recombinant interleukin 21 (IL-21) and goat-derived F(ab)'2 fragments against the human B cell receptor (anti-BCR).

Nephrotic Syndrome Gene Is Required for Endosomal Maturation and Nephrin Endocytosis in .

Background: Variants in cause nephrotic syndrome. TBC1D8B is a GTPase-activating protein for Rab11 (RAB11-GAP) that interacts with nephrin, but how it controls nephrin trafficking or other podocyte functions remains unclear.

Methods: We generated a stable deletion in and used microhomology-mediated end-joining for genome editing.

Selective endocytosis controls slit diaphragm maintenance and dynamics in nephrocytes.

The kidneys generate about 180 l of primary urine per day by filtration of plasma. An essential part of the filtration barrier is the slit diaphragm, a multiprotein complex containing nephrin as major component. Filter dysfunction typically manifests with proteinuria and mutations in endocytosis regulating genes were discovered as causes of proteinuria.

mTOR-Dependent Autophagy Regulates Slit Diaphragm Density in Podocyte-like Nephrocytes.

Both mTOR signaling and autophagy are important modulators of podocyte homeostasis, regeneration, and aging and have been implicated in glomerular diseases. However, the mechanistic role of these pathways for the glomerular filtration barrier remains poorly understood. We used nephrocytes as an established podocyte model and found that inhibition of mTOR signaling resulted in increased spacing between slit diaphragms.