Endosome

Material taken in by endocytosis is delivered first to early (sorting) endosomes just beneath the plasma membrane (pH ≈6.0–6.5). Their mildly acidic lumen, generated by a V-type H⁺-ATPase, makes many ligands dissociate from their receptors. Receptors are then sorted into tubules that return them to the surface directly or via recycling endosomes, while the dissociated ligands remain in the vesicular body.

Early endosomes mature into late endosomes (pH ≈5.0–6.0) as they move inward along microtubules, a switch marked by exchange of Rab5 for Rab7. Membrane proteins destined for degradation, tagged by ubiquitin, are internalised into intraluminal vesicles by the ESCRT machinery, producing multivesicular bodies. Late endosomes receive newly made lysosomal hydrolases from the trans-Golgi network (M6P pathway) and fuse with lysosomes to form endolysosomes, where digestion takes place. When multivesicular bodies fuse with the plasma membrane instead, their intraluminal vesicles are released as exosomes.

Classic examples: LDL binds its receptor in clathrin-coated pits; in the endosome LDL is released and sent to lysosomes (freeing cholesterol), while the receptor recycles about every 10 minutes. Transferrin releases its iron at endosomal pH, and apotransferrin returns to the surface still bound to its receptor. Activated EGF receptors, in contrast, are sent to lysosomes — a way of switching signalling off (receptor down-regulation). Transcytosis carries cargo across epithelia (e.g. IgA, neonatal IgG uptake via FcRn).