The endocytic pathway is a cellular process that brings materials into cells through various mechanisms. From phagocytosis to receptor-mediated endocytosis, this pathway plays a crucial role in nutrient uptake, signal regulation, and immune response.
The secretory pathway, on the other hand, focuses on moving proteins out of cells. It includes both constitutive and regulated secretion, with the Golgi apparatus serving as a central hub for protein modification and sorting before secretion occurs.
Endocytic Pathway
Steps of endocytic pathway
- Endocytosis brings extracellular materials into the cell through various mechanisms
- Phagocytosis engulfs large particles (bacteria, cell debris) by extending pseudopodia around the target
- Pinocytosis uptakes fluids and solutes via smaller vesicles
- Macropinocytosis non-specifically uptakes large amounts of fluid through membrane ruffling
- Clathrin-mediated endocytosis uptakes specific molecules (low-density lipoprotein, transferrin) via clathrin-coated vesicles
- Caveolin-mediated endocytosis uptakes molecules through caveolin-coated vesicles (cholesterol, glycosphingolipids)
- Endocytic vesicle formation occurs by invagination of the plasma membrane followed by pinching off the vesicle into the cytoplasm
- Early endosome serves as the first compartment where endocytic vesicles fuse and deliver their cargo for sorting and recycling or degradation
- Late endosome is an acidic compartment that receives cargo destined for degradation and fuses with lysosomes
- Lysosome contains hydrolytic enzymes that break down macromolecules into their constituent parts (amino acids, simple sugars, nucleotides)
Process of receptor-mediated endocytosis
- Ligand binds to its specific cell surface receptor (insulin, epidermal growth factor)
- Ligand-receptor complexes cluster in clathrin-coated pits, which are regions of the plasma membrane lined with clathrin on the cytoplasmic side
- Clathrin-coated pits invaginate and pinch off to form clathrin-coated vesicles containing the ligand-receptor complexes
- Clathrin coat is removed from the vesicles, which then fuse with early endosomes
- Receptors are sorted in early endosomes for recycling back to the plasma membrane, while ligands are targeted for degradation
- Ligands are delivered to late endosomes and eventually to lysosomes for enzymatic breakdown
Receptor-mediated endocytosis is significant because it allows cells to specifically uptake essential nutrients, regulates signal transduction by controlling cell surface receptor availability, and plays a role in the immune response by facilitating the uptake of antibody-antigen complexes.
Secretory Pathway
Constitutive vs regulated secretory pathways
- Constitutive secretory pathway continuously synthesizes and secretes proteins without storage
- Involves proteins such as extracellular matrix components (collagen, fibronectin) and membrane proteins (receptors, channels)
- Regulated secretory pathway synthesizes and stores secretory products in specialized secretory granules for release upon specific stimuli
- Involves products such as hormones (insulin from pancreatic beta cells) and neurotransmitters (dopamine from neurons)
- Both pathways share common steps: protein synthesis in the rough endoplasmic reticulum (RER), modification and packaging in the Golgi apparatus, and transport of secretory vesicles to the plasma membrane for exocytosis
- The main differences lie in the storage of secretory products and the stimulus-dependent release in the regulated pathway compared to the continuous secretion in the constitutive pathway
Role of Golgi in vesicular trafficking
- Golgi apparatus acts as a central hub for vesicular trafficking and protein modification
- Receives newly synthesized proteins from the RER via COPII-coated vesicles
- Modifies proteins through various processes (glycosylation, sulfation, phosphorylation)
- Sorts and packages modified proteins into appropriate secretory vesicles for transport to their final destination
- Golgi organization facilitates sequential processing and sorting of proteins
- cis-Golgi network (CGN) receives proteins from the RER and initiates modifications
- Golgi stack, composed of flattened cisternae, further modifies and sorts proteins as they move through the stack
- trans-Golgi network (TGN) performs final sorting and packaging of proteins into specific secretory vesicles
- Protein sorting in the TGN is guided by sorting signals on the proteins themselves
- Clathrin-coated vesicles transport proteins destined for endosomes or lysosomes
- Constitutive secretory vesicles transport proteins to the plasma membrane for continuous secretion
- Regulated secretory vesicles (secretory granules) store proteins for release upon specific stimuli