Rer1 Inhibitors

Chemical inhibitors of RER1 function through various mechanisms to disrupt the protein's role in the quality control of integral membrane proteins and the retrieval of endoplasmic reticulum (ER) resident proteins. Brefeldin A directly inhibits RER1 by dismantling the Golgi apparatus structure, which is crucial for RER1's operation. Monensin alters the pH within Golgi compartments, thereby affecting RER1's ability to sort and traffic proteins. Tunicamycin inhibits N-linked glycosylation, a process indirectly connected to RER1, leading to an accumulation of misfolded glycoproteins and increased ER stress that can overload RER1's functionality. Castanospermine and Deoxynojirimycin target glucosidases I and II, essential enzymes for glycoprotein folding. Their inhibition raises ER stress and may overwhelm RER1's capacity to maintain protein quality control, leading to its functional inhibition. Swainsonine impedes mannosidase II, affecting the processing of N-glycans in the Golgi and potentially overwhelming RER1's quality control system due to misfolded glycoproteins.

Kifunensine targets mannosidase I in the ER, creating a backlog in the protein quality control system, indirectly inhibiting RER1. The iminosugar derivative N-(n-Nonyl)deoxynojirimycin also inhibits glucosidases, leading to a buildup of unfolded or misfolded glycoproteins, stressing the ER and RER1's sorting role. Nocodazole and Colchicine disrupt microtubule dynamics, essential for intracellular trafficking, indirectly affecting RER1's function in protein sorting and retrieval. Cytochalasin D acts on actin polymerization, crucial for vesicle movement, potentially affecting RER1's associated trafficking processes. Lastly, Dynasore inhibits the GTPase dynamin, responsible for vesicle scission from membranes, which can lead to reduced vesicular trafficking, indirectly inhibiting RER1's function in protein sorting between the Golgi and ER. Each of these chemicals, by altering specific cellular mechanisms, can impede the function of RER1, highlighting its central role in cellular protein quality control and trafficking pathways.