PMC

CD94/NKG2A intracellular trafficking. The endocytic route of CD94/NKG2A is schematically represented. We have no direct evidence of receptor association with membrane ruffles. The CD94/NKG2A positive vesicles that are formed near the plasma membrane are morphologically similar to macropinosomes in size. However the CD94/NKG2A internalization process does not require actin, dynamin, or Arf6; it is insensitive to PI3K inhibition and PKC stimulation and requires the involvement of Rac1. Thus we arbitrarily termed it a macropinocytic-like process. Upon 15–20 min of endocytosis, the receptor colocalizes with EEA1 and Rab5 and only minimally with Rab4. Co-localization with Rab7 or Rab11 and Lamp-1 or Lamp-2 is never observed indicating that the receptor is recycled back to the plasma membrane without entering the Rab7⁺ or Rab11⁺ compartments (red line) (The color version can be viewed online in the electronic version of the manuscript.)

Schematic representation of the main endocytic pathways. The figure shows the main endocytic pathways and intracellular routes that a receptor can undergo. In the first step of endocytosis a receptor can undergo clathrin-dependent (clathrin-coated pit formation) or clathrin-independent internalization (micro- or macropinocytosis and caveolae-dependent internalization) or a pathway independent from both (GEEC). Following internalization, receptors carried by different vesicles can enter the early (or sorting) endosomes from where they are segregated into separate trafficking itineraries. A receptor can recycle back to the plasma membrane directly from this compartment or after being sorted into the recycling endosome or continue to traffic to the lysosome for the final degradation passing through the endosomal carrier vesicles/multivesicular bodies (ECV/MVBs) and late endosomes. Recycling can also occur at level of late endosomes and lysosomes. Specific markers for each compartment are indicated in red. Recycling pathways are indicated with red lines (The color version can be viewed online in the electronic version of the manuscript.)