Editing Endosome (section)

===Plasma membrane to/from early endosomes (via recycling endosomes)===

Molecules are delivered from the plasma membrane to early endosomes in [[endocytosis|endocytic]] vesicles. Molecules can be internalized via [[receptor-mediated endocytosis]] in [[clathrin]]-coated vesicles. Other types of vesicles also form at the plasma membrane for this pathway, including ones utilising [[caveolae|caveolin]]. Vesicles also transport molecules directly back to the plasma membrane, but many molecules are transported in vesicles that first fuse with recycling endosomes.<ref name="Grant-2009">{{cite journal | vauthors = Grant BD, Donaldson JG | title = Pathways and mechanisms of endocytic recycling | journal = Nature Reviews. Molecular Cell Biology | volume = 10 | issue = 9 | pages = 597–608 | date = September 2009 | pmid = 19696797 | pmc = 3038567 | doi = 10.1038/nrm2755 }}</ref> Molecules following this recycling pathway are concentrated in the tubules of early endosomes. Molecules that follow these pathways include the [[Receptor (biochemistry)|receptors]] for [[LDL]], [[epidermal growth factor]] (EGF), and the iron transport protein transferrin. Internalization of these receptors from the plasma membrane occurs by receptor-mediated endocytosis. LDL is released in endosomes because of the lower pH, and the receptor is recycled to the cell surface. [[Cholesterol]] is carried in the blood primarily by (LDL), and transport by the LDL receptor is the main mechanism by which cholesterol is taken up by cells. EGFRs are activated when EGF binds. The activated receptors stimulate their own internalization and degradation in lysosomes. EGF remains bound to the [[EGF receptor]] (EGFR) once it is endocytosed to endosomes. The activated EGFRs stimulate their own ubiquitination, and this directs them to lumenal vesicles (see below) and so they are not recycled to the plasma membrane. This removes the signaling portion of the protein from the cytosol and thus prevents continued stimulation of growth<ref name="Futter-2001">{{cite journal | vauthors = Futter CE, Collinson LM, Backer JM, Hopkins CR | title = Human VPS34 is required for internal vesicle formation within multivesicular endosomes | journal = The Journal of Cell Biology | volume = 155 | issue = 7 | pages = 1251–64 | date = December 2001 | pmid = 11756475 | pmc = 2199316 | doi = 10.1083/jcb.200108152 }}</ref> - in cells not stimulated with EGF, EGFRs have no EGF bound to them and therefore recycle if they reach endosomes.<ref name="Felder-1990">{{cite journal | vauthors = Felder S, Miller K, Moehren G, Ullrich A, Schlessinger J, Hopkins CR | title = Kinase activity controls the sorting of the epidermal growth factor receptor within the multivesicular body | journal = Cell | volume = 61 | issue = 4 | pages = 623–34 | date = May 1990 | pmid = 2344614 | doi = 10.1016/0092-8674(90)90474-S | s2cid = 22770514 }}</ref> Transferrin also remains associated with its receptor, but, in the acidic endosome, iron is released from the transferrin, and then the iron-free transferrin (still bound to the transferrin receptor) returns from the early endosome to the cell surface, both directly and via recycling endosomes.<ref name="Dautry-Varsat-1986">{{cite journal | vauthors = Dautry-Varsat A | title = Receptor-mediated endocytosis: the intracellular journey of transferrin and its receptor | journal = Biochimie | volume = 68 | issue = 3 | pages = 375–81 | date = March 1986 | pmid = 2874839 | doi = 10.1016/S0300-9084(86)80004-9 }}</ref>