Myeloid-related protein (MRP) 8 and MRP14, calcium-binding proteins of the S100 family, are secreted by activated monocytes via a novel, tubulin-dependent pathway.
Myeloid-related protein (MRP) 8 and MRP14, two members of the S100 family expressed in myelomonocytic cells, have been ascribed some extracellular functions, e.g. antimicrobial, cytostatic, and chemotactic activities. Since S100 proteins lack structural requirements for secretion via the classical endoplasmic reticulum/Golgi route, the process of secretion is unclear. We now demonstrate the specific, energy-dependent release of MRP8 and MRP14 by human monocytes after activation of protein kinase C. This secretory process is not blocked by inhibitors of vesicular traffic through the endoplasmic reticulum and Golgi, and comparative studies on tumor necrosis factor-alpha and interleukin-1beta indicate that MRP8 and MRP14 follow neither the classical nor the interleukin-1-like alternative route of secretion. Inhibition by microtubule-depolymerizing agents revealed that MRP8/MRP14 secretion requires an intact tubulin network. Accordingly, upon initiation of MRP8/MRP14 secretion, immunofluorescence microscopy showed a co-localization of both proteins with tubulin filaments. Release of MRP8 and MRP14 is associated with down-regulation of their de novo synthesis, suggesting that extracellular signaling via MRP8/MRP14 is restricted to distinct differentiation stages of monocytes. Our data provide evidence that the S100 proteins MRP8 and MRP14 are secreted after activation of protein kinase C via a novel pathway requiring an intact microtubule network.
Rammes
A
A
Institute of Experimental Dermatology, University of Münster, 48129 Münster, Germany.
Roth
J
J
Goebeler
M
M
Klempt
M
M
Hartmann
M
M
Sorg
C
C
D000943:Antigens, Differentiation; D020126:Brefeldin A; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D040501:Calgranulin A; D040502:Calgranulin B; D003517:Cyclopentanes / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000523:psychology*; D008954:Models, Biological; D008985:Monensin / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D011487:Protein Conformation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000943:Antigens, Differentiation; D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D040502:Calgranulin B; D003517:Cyclopentanes; D007375:Interleukin-1; D015850:Interleukin-6; D007476:Ionophores; D008070:Lipopolysaccharides; D011500:Protein Synthesis Inhibitors; D014404:Tubulin; D014409:Tumor Necrosis Factor-alpha; D020126:Brefeldin A; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008985:Monensin