• Pinocytosis
• Receptor-mediated endocytosis
• Phagocytosis

• =bulk fluid phase endocytosis
• The random (non-specific) uptake of fluid and molecules in solution. Constitutive process occuring continuously

• The selective uptake and concentration of molecules into coated vesicles
• Small molecules (ligands) bind to plasma membrane receptors that cluster and ligands end up in a coated pi, which pinches off to form a small clathrin-coated vesicle

• Ingestion of large molecules (bacteria, cells) into large vacuoles, which are delivered to lysosomes.
• Macrophages illustrate this process best.
• Kupffer cells and neutrophils are also phagocytes.

• Invagination of Plasma Membrane: Clathrin coated pits, and Caveolae
• Pinching off (formation of  vesicle)
• Acidification of the vesicles destined for digestion
• Fusion of the vesicle with a target

• All clathrin coated pinocytotic vesicles will be direct to the lysosoml pathway leading to digestion of their cargo
• Caveolae deliver their contents to other compartments (e.g. transcytosis in endothelial cell) or to the ER (e.g. in some viral infections)

• sites where lysosomal hydrolases and lysosomal membranes synthesized in RER and Golgi, first combine to enter the endocytic pathway (replacing the former so-called primary lysosome).

• These are characterized by their membrane bound vesicular structures. They can be of various origins but most commonly multivesicular bodies represent an intermediate step between early and late endosomes. They serve as sorting stations in the endocytic pathway.

An inclusion containing material that has not been digested.  It results from a lysosome that has expended its capacity to degrade material.

• Large particle uptake
• Not constitutive process; always triggered by "eat me" signals, balalnce off (+)/(-) signals
• Divided in Heterophagy and Autophagy

• self-eating
• digestion of parts of the cell itself such as organelles
• organelles become surrounded by smooth aread of the rough endoplasmic reticulum to form an AUTOPHAGIC VACUOLE
• the autophagic vacuole fuses with a LATE ENDOSOME to form an AUTOPHAGOLYSOSOME (type of lysosome)
• Indegestible material remains as a residual body

A digestive organelle, limited by a membrane and containing many hydrolytic enzymes. 

Lysosomes have acidic interiors (pH <5) maintained by an ATP-driven proton pump which moves protons (H+) into them. The surrounding membrane also contains other transport proteins, transporting digestion products out of the lysosomes into the cytosol.

Lysosomes are extremely heterogeneous, refelcting their multiple activities.

The Golgi and the trans Golgi network (TGN) play key roles in lysosomal targeting.

            1.         RER

            Site of acid hydrolase synthesis

            2.         GOLGI - cis compartment 

            Receives acid hydrolases from RER via transfer vesicles.

In the cis Golgi compartment, proteins destined for lysosomes are tagged with mannose 6-phosphate groups.

These proteins move through the different Golgi compartments towards the TGN.     

            3.         TGN (trans Golgi network)

Site where acid hydrolases are concentrated and sorted.

Mannose 6-phosphate receptors in the TGN bind the mannose 6-phosphate of the lysosomal hydrolases.  

The hydrolases are concentrated into a clathrin-coated vesicle, which buds off the TGN.

The vesicle loses its clathrin coat, and fuses with a late endosome, where the receptor dissociates from the acid hydrolases. 

A phosphatase removes the phosphate groups from the acid hydrolases, and the receptor recycles back to the TGN.

The late endosome will fuse with material to be digested and thus form a mature lysosome. 

• Accumulation of GM2 (glycolipid components of cell membranes) in the lysosomes of many tissues (particularly in neurons) due to lack of hexosaminidase  A.
• Pathognomonic concentric lamellar deposits in lysosomes of neurons
• Brain (amaurotic familial idiocy, blindness)

Lysosomal enzymes are not tagged with mannose 6-phosphate in the cis Golgi network and therefore are not sorted properly in trans Golgi network by mannose 6-phosphate receptors.  Instead they are secreted and end up in the blood.

Large, swollen, clear lysosomes or with some lamellar inclusions.

Skeletal changes, joint contractures, mental retardation.

• Components: apical canaliculi, vesicles and vacuoules, lysosomes
• This endocytic complex is involved in protein absorption from the glomerular filtrate. When the process becomes overwhelming for the cell it leads to the formation of large phagolysosomes containing both the endocytosed protein as well as autophagocytosed organelles.

• Protein is not excreted normally in the urine. Any protein that isp resent in the filtrate is normally reabsorbed.
• The presence of protein in the urine is a sign of nephron dysfunction.
• The presence of hyaline droplets in tubular epithelial cells is a sign of protein overload.