Collagen Biosynthesis

Intracellular events (STEPS 1-10), extracellular events (STEPS 11-14)

step 1

Formation of mRNA in the nucleus

step 2

Initiation of synthesis of pro-a chains with signal sequences by ribosomes

step 3

synthesis of pro-a chains on the rER

step 4

Hydroxylation of proline anf lysine residues (vitamin C required) and cleavage of signal sequence from pro-a chain

step 5

Glycosylation of specific hydroxylysyl residues in the rER

step 6

formation of procollagen triple helix molecules from a C terminus toward the N terminus in a zipper like manner

step 7

Stabilization of the triple helix by formation of intra- and interchain hydrogen and disulfide bounds and chaperone proteins (e.g., hsp-47)

step 8

Transport of procollagen mlecules to Golgi apparatus

step 9

Packaging of procollagen molecules by Golgi into secretory vesicles

step 10

Movement of vesicles to plasma membrane, assisted by molecular motor proteins associated with microtubules

step 11

Exocytosis of procollagen molecules

step 12

Cleavage of trimeric globular C- and helical N-procollagen domains by procollagen N- and C-proteinases

step 13

Polymerization (self-assembly) of collagen molecules into collagen fibrils (in cove of fibroblast) with development of covalent cross-linking initiated by copper-dependent lysyl oxidase (LOX)

step 14

Incorporation of other collagens (e.g., type V, FACITs, etc.) into collagen fibrils