Every secreted protein passes through a cellular compartment called the Golgi, where it is sorted and loaded into carriers that traffic cargo to the cell surface. To identify new components of this machinery, the Gershlick lab developed CarrierIP, a technique that captures these transient carriers and maps their protein composition. A targeted CRISPR screen in human cells, built from the resulting proteomics data, then identified the genes functionally required for this pathway.
Among the hits was PTPN23, a component of the ESCRT complex not previously linked to secretion. Depletion of PTPN23, alongside ESCRT subunits CHMP1 and VPS4, disrupts carrier fission from the trans-Golgi, blocking cargo delivery to the cell surface. Critically, loss of PTPN23 also impairs the secretion of hormones and antibodies from the specialised cells that produce them, establishing PTPN23 as an essential and previously unrecognised component of the secretory pathway.