Secretion of stem cell regulatory protein Clavata3: when conventional becomes unconventional

Clavata 3 protein (CLV3) is able to control the stem cells development in plants through the maintenance of a fine balance between cell proliferation and differentiation. This protein cooperates with Wus protein by a negative feedback in the plant apical meristem. CLV3 is a secretory protein of 35 kDa. It has an N-terminal signal peptide, which permits its traslocation into the endoplasmatic reticulum (ER) and the active mature CLV3 is a dodecapeptide (called CLE domain) released after proteolysis. It is believed that CLV3, after insertion in the ER, enters in the classic secretory pathway and transits through the Golgi apparatus before being secreted in the apoplast. Once outside the cell, it undergoes a proteolytic maturation process with the production of the active dodecapeptide. This peptide links the CLAVATA1- CLAVATA2 heterodimer complex on the plasma membrane starting a cascade process which, at the end, causes WUS inactivation. Here we propose a new mechanism of CLV3 transport in which, after the insertion in the ER, the protein is retro-translocated within the cytosol. In this compartment, CLV3 undergoes a controlled digestion by the proteasome and then the active dodecapeptides are unconventionally secreted outside the cell. The secretion of this protein, which has a signal peptide, could be an important example of the possible alternatives to the classical secretion route.