To study retrieval from lysosomes in living cells, Mellman and colleagues made an MHC-II–green fluorescent protein (GFP) fusion protein (shown in green in the figure). MHC-II–GFP recapitulated the dynamic localization pattern of endogenous MHC-II, residing in the lysosomes of immature DCs (left, shown in red) and then rapidly redistributing to the plasma membrane after maturation (right).
So how do the MHC II complexes escape the lysosomes and move to the cell surface? Previous work has shown that activation of DC-like cells (J. Cell Biol. 155, 53–63 (2001)) coincides with a marked tubulation of lysosomal membranes. Thus, it was speculated that these tubules might aid transport to the plasma membrane. Using MHC-II–GFP, Mellman and colleagues imaged DCs during maturation and observed that the lysosomal structures underwent marked morphological changes, forming long tubules. As they looked in more detail, they noticed that these tubules were transient, separating off and moving towards the cell surface. Interestingly, most of the lysosomal content was excluded from the tubules, suggesting that the movement of MHC II molecules out of lysosomes is selective and regulated.
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