Vesicular Protein Sorting in the Secretory and Endocytic pathway – Cellular Communication & Lysosome Biogenesis
Vesicular protein transport in the secretory and endocytic pathway is facilitated by cytoplasmic proteins called adaptors, which bind specifically to membranes and to the cytoplasmic domains of cargo proteins. They recruit a number of cytoplasmic proteins to the site of transport vesicle formation. There is a family of 5 homologous heterotetrameric adaptor-protein complexes in higher eukaryotes: AP-1, AP-2, AP-3, AP-4 and AP-5. Only AP-1 & AP-2 form clathrin-coated-vesicles. They are ubiquitously expressed and tissue specific isoforms exist of AP-1, AP-2 and AP-3. Their precise functions and molecular mechanisms in regulating protein sorting, transport vesicle formation and vesicular trafficking are poorly understood.
We are focusing on the AP-1 complex. Eight tissue-specific AP-1 isoforms exist besides two ubiquitous complexes, by far the largest family of AP-complexes. It is required for protein sorting in the trans-Golgi Network and endosomes, and also controls protein sorting to the plasma membrane. We are using AP-1 adaptin mouse ‘knock-out’ models and cell lines derived from these to study their functions and molecular mechanisms, focusing on brain functions.