Modulation of secretory granule-targeting efficiency by cis and trans compounding of sorting signals.
Several protein domains acting through seemingly different mechanisms have been reported to have the capacity to target proteins to dense core secretory granules. Because proteins enter secretory granules with different efficiencies and because some of these proteins contain more than one granule-targeting motif, we have investigated whether compounding sorting signals could alter the efficiency of protein entry into secretory granules. In the current study we demonstrate that a paired basic cleavage site from human prorenin and an alpha-helix-containing secretory granule-sorting signal from the prohormone convertase PC1/3 can synergize to increase granule-sorting efficiency not only when located on the same protein, but also when located on distinct proteins that associate in the secretory pathway.
Lacombe
Marie-Josée
MJ
Laboratory of Molecular Biochemistry of Hypertension, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada.
Mercure
Chantal
C
Dikeakos
Jimmy D
JD
Reudelhuber
Timothy L
TL
D000818:Animals; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000494:pharmacology; D019281:Dimerization; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D010957:Plasmids / Q000378:metabolism; D045664:Proprotein Convertase 1 / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D012083:Renin / Q000737:chemistry*; D022142:Secretory Vesicles / Q000502:physiology*; D014162:Transfection
D003432:Cross-Linking Reagents; D045664:Proprotein Convertase 1; D012083:Renin