The N-terminal fragment of Reelin is generated after endocytosis and released through the pathway regulated by Rab11.
Reelin is a large secreted glycoprotein essential for brain formation, but its trafficking and function at the molecular level remain incompletely understood. After binding to its receptor, Reelin is internalized by endocytosis. Here we show that internalized Reelin is subject to specific proteolysis within the cell and its N-terminal fragment is re-secreted. This re-secretion is inhibited by bafilomycin A(1) or by expression of a mutant of Rab11, a regulator of the recycling pathway. As the N-terminal fragment does not bind to Reelin receptor but has homology to F-spondin, its recycling may be involved in the regulation of extracellular matrix.
Hibi
Terumasa
T
Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
Hattori
Mitsuharu
M
D000818:Animals; D015153:Blotting, Western; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D006868:Hydrolysis; D018942:Macrolides / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000737:chemistry*; D020691:rab GTP-Binding Proteins / Q000502:physiology*; D000099193:rab11 GTP-Binding Proteins
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D018942:Macrolides; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C057620:bafilomycin A; C000717128:Reln protein, mouse