Constipation kills

Cellular constipation can be deadly, according to a study on page 1587. Wang and colleagues show that cells get clogged with aborted secretory cargo when they lack an enzyme that helps form vesicles. Deletion of this enzyme proved lethal in mice, halting brain, bone and vascular development.

The enzyme in question is a protein tyrosine phosphatase (PTP) called MEG2. MEG2 binds lipids and resides on intracellular vesicle membranes, where it clips phosphate residues from the fusion protein NSF. Once dephosphorylated, NSF initiates homotypic fusion between immature secretory vesicles, a critical step in protein secretion.

Knocking out MEG2, the team found, prevented T cells (isolated from chimeric mice) from secreting the autocrine growth factor interleukin-2, stunting T cell proliferation in response to stimulation. Electron micrographs of the deficient T cells revealed that...