Dependence on pH of polarized sorting of secreted proteins.
The plasma membranes of epithelial cells are divided into apical and basolateral domains. These two surfaces are characterized by markedly different protein compositions, reflecting the ability of the cell to target newly synthesized membrane proteins to specific regions of the cell surface. This targeting capability is also apparent in the polarized release of secretory products. Recent studies using canine renal tubule (MDCK) cells have suggested that distinct sets of secretory proteins are released from their apical and basolateral poles. We report experiments designed to examine secretory protein sorting by MDCK cells. We have shown that secretion of basement membrane components (laminin and heparan sulphate proteoglycan (HSPG] takes place from the basolateral cell surface and that this polarized release results from active sorting. The sorting process which mediates this polarized secretion requires an acidic intracellular compartment. MDCK cells treated with NH4Cl to raise the pH of their intracellular compartments, secrete laminin and HSPG by a default pathway which leads to their release in roughly equal quantities into the medium of both the apical and basolateral compartments.
Caplan
M J
MJ
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.
Stow
J L
JL
Newman
A P
AP
Madri
J
J
Anderson
H C
HC
Farquhar
M G
MG
Palade
G E
GE
Jamieson
J D
JD
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D004285:Dogs; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007684:Kidney Tubules / Q000648:ultrastructure; D007797:Laminin / Q000378:metabolism; D008970:Molecular Weight; D011506:Proteins / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000643:Ammonium Chloride; D002402:Cathepsin D; D011508:Chondroitin Sulfate Proteoglycans; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D007797:Laminin; D011506:Proteins; D000254:Sodium-Potassium-Exchanging ATPase