Lysosome Biogenesis

Biogenesis
The formation of the lysosome is one of the main functions of the Golgi apparatus. Glycosilated lysosomal proteins are transferred from the endoplasmic reticulum to the cis Golgi netwok.These proteins have on their surface a cluster of neighbouring amino acids known as a signal patch. This is the signal for adding the M6P units to the oligosaccharides of the lysosomal hydrolase. Thisprocess is catalyzed by two enzymes which are the GlcNAc phosphotransferase and the N-Acetylglucosaminidase.
The recognition site of the GlcNAc phosphotransferase enzyme binds to the signal patchof the lysosomal hydrolase. The catalytic site of this enzyme binds both the high mannose N-linked oligosaccharide and UDP-GlcNAc. However, only one part of the UDP-GlcNAc, the GlcNAc phosphate, bindsto the manose.
The second enzyme, N-Acetylglucosaminidase will cleave off the GlcNAc leaving the M6P exposed in the trans Golgi.
Since lysosomal hydrolases contain multiple oligosaccharides theyacquire many M6P residues, providing high affinity signal for the M6P receptors. This is how lysosomal proteins are recognized in the trans Golgi network. Due to this specific recognition, the lysosomalhydrolases are packaged into clathrin-coated vesicles that will then emerge towards the early endosome.
The classical clatrin mediated pathway is the best known pathway, but there are more differententries into the cell. The vesicles shed their coat and deliver their contents fusing to early endosomes. Then the acid phosphatase will remove the phosphate group from the manose destroying thesorting signal and hence contributing to the release of the lysosomal hydrolase from the M6P receptor. This ensures that the lysosomal hydrolases do not return to the Golgi apparatus with the receptor.This process occurs at a low pH.
Empty receptors are recycled in retromer-coated vesicles to the Golgi apparatus for futher rounds of transports.
Vesicles are transported from the TGN to the early...