A PTPN23-dependent ESCRT pathway is essential for constitutive secretion in mammalian cells
Year: 2026
Type: article
Abstract: Secreted proteins are essential for processes like immune responses, cellular communication, and extracellular matrix remodeling. Once synthesized 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 analyzed post-Golgi carriers by mass spectrometry. Candidate machinery was subsequently assessed in 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 specialized cells. We propose that PTPN23 is essential for secretion from the trans-Golgi.
Source: The Journal of Cell Biology
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: hybrid
Awards: G2146881008, Mapping and characterising constitutive secretion in human neurons, Spatiotemporally resolved proteomics of protein trafficking pathways, TRR 186: Molekulare Schalter zur räumlichen und kinetischen Regulation der zellulären Signaltransmission, How does the Golgi sort proteins? Mapping the Biophysical Landscape of the Secretory Pathway, Enabling technologies, Spatiotemporally resolved proteomics of protein trafficking pathways, G6432094593
OpenAlex ID: W7138865583