Meeting of conventional and unconventional pathways at the TGN

The biosynthetic pathway allows the transport of newly synthesized proteins to the TGN via the reticulum endoplasmic and Golgi apparatus. However, many large particles reach the TGN by unconventional means. For instance, Herpes simplex virus type 1(HSV-1) capsids assemble within the nucleus, bud into the perinuclear space, fuse with the outer nuclear membrane and finally travel unenveloped towards the TGN. Given the central role of protein kinase D in the transport of small cargo from the TGN to the cell surface, we probed its potential contribution in HSV-1 egress, as a model for studying large cargo exiting from the TGN. Using a synchronized infection, we show that inactivation of protein kinase D with pharmacological inhibitors, a kinase dead mutant or siRNA all causes the retention of HSV-1 at the TGN. This highlights the role of PKD in viral exit and a dependence of the virus on the classical host cell machinery to leave the TGN, unlike its previous transport steps. Conceptually, this supports a model in which the TGN is a meeting point where conventional and unconventional routes encounter.