Secreted proteins are essential for processes like immune responses, cellular communication, and extracellular matrix remodeling. Once synthesised and processed at the Golgi, some of these proteins are packaged for delivery to the plasma membrane. While this transport and sorting rely on complex molecular machinery, the precise mechanisms remain unclear. In this study, we affinity-isolated and analysed post-Golgi carriers through mass spectrometry, followed by a pooled CRISPR-KO screen. This led to the identification of a rich set of new genes functionally important for Golgi-to-plasma membrane delivery including PTPN23, a component of the endosomal sorting complex required for transport (ESCRT) complex. Depletion of PTPN23, as well as the ESCRT subunits CHMP1 and VPS4, disrupts tubule fission from the trans-Golgi, impairing cargo delivery to the surface. Furthermore, the loss of PTPN23 also prevents the constitutive secretion of soluble cargoes, and of endogenous hormones and antibodies in specialised cells. We propose that PTPN23 is essential for secretion from the trans-Golgi.
Stalder et al. (Tue,) studied this question.