Second-messenger regulation of receptor association with clathrin-coated pits: a novel and selective mechanism in the control of CD4 endocytosis

Autor: Karl-Heinz Krause, Michelangelo Foti, Didier Trono, Christopher Aiken, Jean-Louis Carpentier, Daniel Pablo Lew
Rok vydání: 1997
Předmět:
Coated Pits
Cell-Membrane/drug effects/ physiology/ultrastructure
Insulin/metabolism
media_common.quotation_subject
Endocytosis/drug effects/ immunology
Receptors
Cell Surface
HL-60 Cells
Transferrin receptor
Pertussis toxin
Endocytosis
Second Messenger Systems
Clathrin
chemistry.chemical_compound
Cyclic AMP
Insulin
Humans
Src-Family Kinases/metabolism
Internalization
Receptor
Cyclic AMP/pharmacology
Molecular Biology
media_common
ddc:616
Forskolin
biology
Antigens
CD4/drug effects/ metabolism
Transferrin
Receptors
Cell Surface/ physiology
Coated Pits
Cell-Membrane
Cell Biology
Transferrin/drug effects/metabolism
Cell biology
Insulin receptor
src-Family Kinases
Second Messenger Systems/ physiology
chemistry
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
CD4 Antigens
biology.protein
Research Article
Zdroj: Molecular Biology of the Cell, Vol. 8, No 7 (1997) pp. 1377-1389
ISSN: 1939-4586
1059-1524
DOI: 10.1091/mbc.8.7.1377
Popis: CD4, a member of the immunoglobulin superfamily, is not only expressed in T4 helper lymphocytes but also in myeloid cells. Receptor-mediated endocytosis plays a crucial role in the regulation of surface expression of adhesion molecules such as CD4. In T lymphocytes p56lck, a CD4-associated tyrosine kinase, prevents CD4 internalization, but in myeloid cells p56lck is not expressed and CD4 is constitutively internalized. In this study, we have investigated the role of cyclic AMP (cAMP) in the regulation of CD4 endocytosis in the myeloid cell line HL-60. Elevations of cellular cAMP were elicited by 1) cholera toxin, 2) pertussis toxin, 3) forskolin and IBMX, 4) NaF, or 5) the physiological receptor agonist prostaglandin E1. All five interventions led to an inhibition of CD4 internalization. Increased cAMP levels did not inhibit endocytosis per se, because internalization of insulin receptors and transferrin receptors and fluid phase endocytosis were either unchanged or slightly enhanced. The mechanism of cAMP inhibition was further analyzed at the ultrastructural level. CD4 internalization, followed either by quantitative electron microscopy autoradiography or by immunogold labeling, showed a rapid and temperature-dependent association of CD4 with clathrin-coated pits in control cells. This association was markedly inhibited in cells with elevated cAMP levels. Thus these findings suggest a second-messenger regulation of CD4 internalization through an inhibition of CD4 association with clathrin-coated pits in p56lck-negative cells.
Databáze: OpenAIRE
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