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Secretion and lysophospholipase D activity of autotaxin by adipocytes are controlled by N-glycosylation and signal peptidase.: Secretion and Activity of Adipocyte Autotaxin

Abstract : Autotaxin (ATX) is a lysophospholipase D involved in synthesis of lysophosphatidic acid (LPA). ATX is secreted by adipocytes and is associated with adipogenesis and obesity-associated diabetes. Here we have studied the mechanisms involved in biosynthesis and secretion of ATX by mouse 3T3-F442A adipocytes. We found that inhibition of N-glycosylation with tunicamycin or by double point deletion of the amino-acids N53 and N410 of ATX inhibit its secretion. In addition, N-glycosidase treatment and point deletion of the amino-acid N410 inhibits the lysophospholipase D activity of ATX. Analysis of the amino-acid sequence of mouse ATX shows the presence of a N-terminal signal peptide. Treatment with the signal peptidase inhibitor globomycin inhibits ATX secretion by adipocytes. Transfection in Cos-7 cells of site-directed deleted ATX shows that ATX secretion is dependent on the hydrophobic core sequence of the signal peptide, not on the putative signal peptidase cleavage site sequence. Analysis of the amino-acid sequence of mouse ATX also reveals the presence of a putative cleavage site by the protein convertase furin. Treatment of adipocytes with the furin inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethylketone does not modified secretion or lysophospholipase D activity of ATX. Transfection in Cos-7 cells of site-directed deleted ATX shows that the furin recognition site is not required for secretion or lysophospholipase D activity of ATX. In conclusion, the present work demonstrates the crucial role of N-glycosylation in secretion and activity of ATX. The present work also confirms the crucial role signal peptidase in secretion of ATX by adipocytes.
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https://www.hal.inserm.fr/inserm-00115644
Contributor : Jean Sébastien Saulnier-Blache <>
Submitted on : Thursday, December 14, 2006 - 11:48:11 AM
Last modification on : Friday, January 10, 2020 - 9:09:03 PM
Long-term archiving on: : Tuesday, April 6, 2010 - 7:53:52 PM

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Jean-Philippe Pradère, Evelyne Tarnus, Sandra Grès, Philippe Valet, Jean Sébastien Saulnier-Blache. Secretion and lysophospholipase D activity of autotaxin by adipocytes are controlled by N-glycosylation and signal peptidase.: Secretion and Activity of Adipocyte Autotaxin. BBA - Biochimica et Biophysica Acta, Elsevier, 2007, 1771 (1), pp.93-102. ⟨10.1016/j.bbalip.2006.11.010⟩. ⟨inserm-00115644⟩

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