The Late Endosomal Transporter CD222 Directs the Spatial Distribution and Activity of Lck

The spatial and temporal organization of T cell signaling molecules is increasingly accepted as a crucial step in controlling T cell activation. CD222, also known as the cation-independent mannose 6-phosphate/insulin-like growth factor 2 receptor, is the central component of endosomal transport pathways. In this study, we show that CD222 is a key regulator of the early T cell signaling cascade. Knockdown of CD222 hampers the effective progression of TCR-induced signaling and subsequent effector functions, which can be rescued via reconstitution of CD222 expression. We decipher that Lck is retained in the cytosol of CD222-deficient cells, which obstructs the recruitment of Lck to CD45 at the cell surface, resulting in an abundant inhibitory phosphorylation signature on Lck at the steady state. Hence, CD222 specifically controls the balance between active and inactive Lck in resting T cells, which guarantees operative T cell effector functions

Crystal structure of Lon protease: molecular architecture of gated entry to a sequestered degradation chamber

The prototypical ATP-dependent protease Lon, like many other AAA+ ATPases, has proven notoriously resilient to crystallographic analysis. The first high-resolution structure of the intact hexameric enzyme now unveils its closed degradation chamber and its gating