Antibody to the phosphomannosyl receptor inhibits recycling of receptor in fibroblasts.
The 215-kd phosphomannosyl receptor is involved in the transport of newly synthesized acid hydrolases to lysosomes and also mediates the pinocytosis of lysosomal enzymes by fibroblasts in culture. Recycling of receptors to the sorting sites is an integral part of both these processes. In this report, we describe the inhibition in human fibroblasts of both functions of the phosphomannosyl receptor by a rabbit antiserum to the bovine liver receptor. This inhibition cannot be completely accounted for by inhibition of ligand-receptor interaction. Rather the antibody appears to cross-link receptors and cause a removal of receptors from the sorting sites (plasma membrane and Golgi apparatus) and their accumulation in a compartment from which they do not recycle. Removal of receptors from the recycling pool by antibody is irreversible, and return of receptors requires synthesis of new protein. Degradation of "trapped receptors" is enhanced (t1/2 = 7.5 hr), but much more gradual than their removal from the functional receptor pool (t1/2 = 30 min).
Nolan
C M
CM
EA Doisy Department of Biochemistry, St Louis University School of Medicine, Missouri 63104.
Creek
K E
KE
Grubb
J H
JH
Sly
W S
WS
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005966:Glucuronidase / Q000378:metabolism; D006041:Goats; D006801:Humans; D006867:Hydrolases / Q000378:metabolism*; D010873:Pinocytosis; D011817:Rabbits; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D013661:Tay-Sachs Disease / Q000201:enzymology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D000906:Antibodies; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; C034304:cation-dependent mannose-6-phosphate receptor; D006867:Hydrolases; D005966:Glucuronidase; D001619:beta-N-Acetylhexosaminidases