Loss of ARPC1B impairs cytotoxic T lymphocyte maintenance and cytolytic activity.

CD8 cytotoxic T lymphocytes (CTLs) rely on rapid reorganization of the branched F-actin network to drive the polarized secretion of lytic granules, initiating target cell death during the adaptive immune response. Branched F-actin is generated by the nucleation factor actin-related protein 2/3 (Arp2/3) complex. Patients with mutations in the actin-related protein complex 1B (ARPC1B) subunit of Arp2/3 show combined immunodeficiency, with symptoms of immune dysregulation, including recurrent viral infections and reduced CD8+ T cell count.

Analysis of the Retromer complex-WASH complex interaction illuminates new avenues to explore in Parkinson disease.

The retromer complex mediates endosomal protein sorting by concentrating membrane proteins (cargo) into nascent tubules formed through the action of sorting nexin (SNX) proteins. The WASH complex is recruited to endosomes by binding to the VPS35 subunit of retromer and facilitates cargo protein sorting by promoting formation of endosomally-localized F-actin. The VPS35 protein is mutated in Parkinson disease (PD) and a recent report has revealed that the PD-causing mutation impairs the association of retromer with the WASH complex leading to perturbed endosomal protein sorting.

Loss of the Batten disease gene CLN3 prevents exit from the TGN of the mannose 6-phosphate receptor.

The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are a group of inherited childhood-onset neurodegenerative disorders characterized by the lysosomal accumulation of undigested material within cells. To understand this dysfunction, we analysed trafficking of the cation-independent mannose 6-phosphate receptor (CI-MPR), which delivers the digestive enzymes to lysosomes. A common form of NCL is caused by mutations in CLN3, a multipass transmembrane protein of unknown function.