Grant: CIHR Fellowship

Cells within complex organisms such as humans are comprised of several distinct compartments called organelles, each of which is responsible for distinct cellular functions. Vesicle transport is a process that moves proteins and lipids from one organelle to another to ensure that they have the right components to function properly. For example, when cells receive a signal to grow, vesicle transport ensures that the correct amount of a receptor protein is at the cell surface to receive the signal. This is done either by delivering it from other organelles, or by removing it from the cell surface. Within the vesicle transport system, groups of proteins called endocytic transport complexes regulate where these vesicles are sent. However, while a number of these complexes have been identified and characterized, methods of directing vesicle transport are still largely unknown. Two human proteins called LEPROT and LEPROTL1 have recently been shown to promote growth hormone receptor removal from the cell surface, while LEPROT also affects the obesity receptor to regulate cell weight. A protein very similar to LEPROT and LEPROTL1 exists in yeast called Vps55. This protein forms a complex with Vps68, and together they regulate transport between organelles conferring destruction or recycling of the vesicular components. Thus, Vps55 and 68 likely form a novel endocytic sorting complex in yeast. Two proteins very similar to Vps68 (TMEM50A and TMEM50B) exist in humans, and likely form complexes with LEPROT and LEPROTL1 with similar functions. My research aims to identify all the proteins functioning within these complexes and how they regulate endocytic transport. Given the central role of vesicle transport in cellular activities, and that LEPROT and LEPROTL1 regulate growth and obesity, the outcomes of this research are expected to have a great impact on health and disease.