In this thesis I explored the ins and outs of the multivesicular body, the pathways that intersect at this central endocytic compartment, the dynamics governing its lumen and how such processes... Show moreIn this thesis I explored the ins and outs of the multivesicular body, the pathways that intersect at this central endocytic compartment, the dynamics governing its lumen and how such processes impact various fields of cell biology and disease. Show less
Dit proefschrift bevat onderzoek over verschillende processen binnen het intracellulaire domein. Als eerst wordt er onderzocht hoe een cel zijn oplosbare eiwitten in de correcte compartimenten... Show moreDit proefschrift bevat onderzoek over verschillende processen binnen het intracellulaire domein. Als eerst wordt er onderzocht hoe een cel zijn oplosbare eiwitten in de correcte compartimenten krijgt na mitosis. Het tweede omschrijft een mechanisme dat verantwoordelijk is voor het structureren van het endoplasmatisch reticulum. Als derde werd onderzocht wat voorn rol het eiwit MOSPD2 vervult binnen contacten tussen het ER, Golgi apparatus en lysosomen. Show less
Calcium is the third most abundant metal on earth, and the fundaments of its homeostasis date back to pre-eukaryotic life forms. In higher organisms, Ca2+ serves as a cofactor for a wide array of ... Show moreCalcium is the third most abundant metal on earth, and the fundaments of its homeostasis date back to pre-eukaryotic life forms. In higher organisms, Ca2+ serves as a cofactor for a wide array of (enzymatic) interactions in diverse cellular contexts and constitutes the most important signaling entity in excitable cells. To enable responsive behavior, cytosolic Ca2+ concentrations are kept low through sequestration into organellar stores, particularly the endoplasmic reticulum (ER), but also mitochondria and lysosomes. Specific triggers are then used to instigate a local release of Ca2+ on demand. Here, communication between organelles comes into play, which is accomplished through intimate yet dynamic contacts, termed membrane contact sites (MCSs). The field of MCS biology in relation to cellular Ca2+ homeostasis has exploded in recent years. Taking advantage of this new wealth of knowledge, in this Review, we invite the reader on a journey of Ca2+ flux through the ER and its associated MCSs. New mechanistic insights and technological advances inform the narrative on Ca2+ acquisition and mobilization at these sites of communication between organelles, and guide the discussion of their consequences for cellular physiology. Show less
