Trafficking/sorting and granule biogenesis in the beta-cell.
Proinsulin is packaged into nascent (immature, clathrin-coated) secretory granules in the trans-Golgi network (TGN) of the beta -cell along with other granular constituents including the proinsulin conversion enzymes. It is assumed that such packaging is dependent on an active sorting process, separating granular proteins from other secretory or membrane proteins, but the mechanism remains elusive. As granules mature, the clathrin coat is lost, the intragranular milieu is progressively acidified, and proinsulin is converted to insulin and C-peptide. Loss of clathrin is believed to arise by budding of clathrin-coated vesicles from maturing granules, carrying with them any inappropriate or unnecessary products and providing an additional means for refinement of granular content.
Molinete
M
M
Louis-Jeantet Research Laboratories, University Medical Center, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.
Irminger
J C
JC
Tooze
S A
SA
Halban
P A
PA
D000818:Animals; D001693:Biological Transport, Active; D002966:Clathrin / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000378:metabolism* / Q000648:ultrastructure; D008563:Membrane Lipids / Q000378:metabolism; D011384:Proinsulin / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*
D002966:Clathrin; D007328:Insulin; D008563:Membrane Lipids; D011384:Proinsulin