Receptor may not be present at all o receptor may be

This preview shows page 8 - 10 out of 14 pages.

Receptor may not be present at all o Receptor may be defective – in either binding of LDL or AP2 o Or LDL receptors may be functional and present, but fail to accumulate in clathrin-coated pits Receptors enter pits, regardless of whether specific ligand has bound or not in many cases (LDL is an example) Specific Proteins are Retrieved from Early Endosomes and Returned to the Plasma Membrane In early endosome, LDL receptor dissociates from its ligand LDL and is recycled back to plasma membrane for reuse o Recycling transport vesicles bud from long, narrow tubes that extend from endosomes Transferrin receptor, unlike LDL receptor, recycles its ligand
o Transferrin is a soluble protein that carries iron in the blood o Transferrin receptors deliver transferrin with its bound iron to early endosomes via receptor-mediated endocytosis, where endosomes’s low pH encourages transferrin to release its iron o Apotransferrin (iron-free transferrin)-receptor complex are both recycled back to plasma membrane o Apotransferrin dissociates from its receptor free to pick up more iron and be used again o In summary, the transferrin avoids lysosomes Plasma Membrane Signaling Receptors are Down-regulated by Degradation in Lysosomes EGF receptors accumulate in clathrin-coated pits only after binding to its ligand and are degraded in lysosomes along with their ligand EGF o EGF binding intracellular signaling pathway that leads to decrease in concentration of EGF receptors …..called receptor downregulation – reduces cell’s subsequent sensitivity to EGF Receptor downregulation is highly regulated o Activated receptors are covalently modified with mono/multiubiquitylation o Ubiquitin-binding proteins recognize the attached ubiquitin and help direct modified receptors into clathrin-coated pits o ESCRT complexes (another type of ubiquitin-binding protein) recognize and sort the ubiquitylated receptors into MVBs in the early endosome degradation Early Endosome Matures into Late Endosome Early endosomes have tubular and vacuolar domains o During endosome maturation, vacuolar portions are retained and transformed into late endosomes while tubular portions shrink o Multivesicular bodies (aka maturing endosomes) concentrate in perinuclear region of cell and fuse with one another and eventually with endolysosomes/lysosomes Many changes occur during maturation process o 1. Endosome changes shape and location – tubular domains lost, vacuolar domains are thoroughly modified o 2. Rab proteins, PI lipids, fusion machinery (SNAREs and tethers), and microtubule motor proteins involved in changing cytosolic face of endosome membrane o 3. V-type ATPase pumps H+ from cytosol into endosome lumen to acidify organelle o 4. Intralumenal vesicles sequester endocytosed signaling receptors inside endosome –halting receptor signaling activity o 5. Lysosome proteins are delivered from the TGN to maturing endosome

  • Left Quote Icon

    Student Picture

  • Left Quote Icon

    Student Picture

  • Left Quote Icon

    Student Picture