9.B.191 The Endoplasmic Reticulum Retention Receptor (KDELR) Family
The endoplasmic reticulum (ER)-Golgi system has been studied using biochemical, genetic, electron and light microscopic techniques leading to an understanding of many aspects of trafficking from the ER to the Golgi apparatus (Murshid and Presley 2004). This includes some of the signals and mechanisms for selective retention and retrieval of ER resident proteins and export of cargo proteins. Proteins that leave the ER emerge in 'export complexes' or ER 'exit sites' and accumulate in pleiomorphic transport carriers referred to as VTCs or intermediate compartments. These structures then transit from the ER to the Golgi apparatus along microtubules using the dynein/dynactin motor and fuse with the cis cisterna of the Golgi apparatus. Many proteins (including vSNAREs, ERGIC53/p58 and the KDEL receptor) must cycle back to the ER from pre-Golgi intermediates or the Golgi. Murshid and Presley 2004 considered a model suggesting that this cycling occurs via 50-nm COPI-coated vesicles and in vivo evidence that suggests that retrograde trafficking may occur via tubular structures. Intracellular membrane transport involves the coordinated engagement of a series of organelles and molecular machineries that ensure that proteins are delivered to their correct cellular locations.
Due to its central position in the secretory pathway and to the large amounts of signaling molecules associated with it, the Golgi complex plays a role in this regulation. The generation of autonomous signaling by the Golgi complex in response to the arrival of cargo from the endoplasmic reticulum (ER) allows that cargo moving from the ER to the Golgi activates a series of signaling pathways. This regulatory mechanism is called the Golgi control system (Cancino et al. 2013). A key player in this control system is the KDEL receptor, which retrieves chaperones back to the endoplasmic reticulum and behaves as a signaling receptor. The KDEL receptor regulates pathways involved in the maintenance of the homeostatic transport apparatus, in particular, of the Golgi complex.