Bottanelli group – Membrane trafficking

Despite significant advances in identifying the machinery and molecular mechanisms involved in cargo sorting at the trans-Golgi network (TGN), we know little about the sub-compartmental nanodomain organization of the TGN that likely underlies the spatio-temporally controlled sorting of distinct cargos to different organelles or plasma membrane domains. Sorting at the TGN is particularly important, yet remains poorly understood, in polarized cells, where it is unknown whether apical and basolateral cargoes segregate at the level of the TGN or in downstream endosomal compartments. The Bottanelli lab employs state-of-the-art imaging techniques to understand how sorting is realized at the nanoscale level and in living cells. In particular we use stimulated emission depletion (STED) imaging and CRISPR/Cas9 knock-ins to study how the coordinated action of various molecular switches and membrane scaffolds drives the fidelity of cargo sorting at the TGN.

The TGN is a crucial sorting station along the secretory pathway. The TGN (red) sorts cargoes into transport carriers for the apical and basolateral PM either directly [1a-2a] or via apical recycling endosomes (ARE; blue) [1b] and perinuclear recycling endosomes (PRE; magenta) [2b], the endo-lysosomal system (yellow) [3] and earlier Golgi cisternae [4].

Super-resolution highlights the organization of the adaptor protein complex 1 (AP-1) in nano-domains (magenta) on the TGN (green). Scale bars are 2 µm and 1 µm in the cropped images