PMID- 19780201 OWN - NLM STAT- MEDLINE DCOM- 20100308 LR - 20220317 IS - 1098-1136 (Electronic) IS - 0894-1491 (Linking) VI - 58 IP - 3 DP - 2010 Feb TI - Differential vesicular distribution and trafficking of MMP-2, MMP-9, and their inhibitors in astrocytes. PG - 344-66 LID - 10.1002/glia.20927 [doi] AB - Astrocytes play an active role in the central nervous system and are critically involved in astrogliosis, a homotypic response of these cells to disease, injury, and associated neuroinflammation. Among the numerous molecules involved in these processes are the matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, secreted or membrane-bound, that regulate by proteolytic cleavage the extracellular matrix, cytokines, chemokines, cell adhesion molecules, and plasma membrane receptors. MMP activity is tightly regulated by the tissue inhibitors of MMPs (TIMPs), a family of secreted multifunctional proteins. Astrogliosis in vivo and astrocyte reactivity induced in vitro by proinflammatory cues are associated with modulation of expression and/or activity of members of the MMP/TIMP system. However, nothing is known concerning the intracellular distribution and secretory pathways of MMPs and TIMPs in astrocytes. Using a combination of cell biology, biochemistry, fluorescence and electron microscopy approaches, we investigated in cultured reactive astrocytes the intracellular distribution, transport, and secretion of MMP-2, MMP-9, TIMP-1, and TIMP-2. MMP-2 and MMP-9 demonstrate nuclear localization, differential intracellular vesicular distribution relative to the myosin V and kinesin molecular motors, and LAMP-2-labeled lysosomal compartment, and we show vesicular secretion for MMP-2, MMP-9, and their inhibitors. Our results suggest that these proteinases and their inhibitors use different pathways for trafficking and secretion for distinct astrocytic functions. CI - (c) 2009 Wiley-Liss, Inc. FAU - Sbai, Oualid AU - Sbai O AD - Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, UMR 6184 CNRS--Universite de la Mediterranee, Faculte de Medecine, 51 Boulevard Pierre Dramard, Marseille Cedex 15, France. FAU - Ould-Yahoui, Adlane AU - Ould-Yahoui A FAU - Ferhat, Lotfi AU - Ferhat L FAU - Gueye, Yatma AU - Gueye Y FAU - Bernard, Anne AU - Bernard A FAU - Charrat, Eliane AU - Charrat E FAU - Mehanna, Ali AU - Mehanna A FAU - Risso, Jean-Jacques AU - Risso JJ FAU - Chauvin, Jean-Paul AU - Chauvin JP FAU - Fenouillet, Emmanuel AU - Fenouillet E FAU - Rivera, Santiago AU - Rivera S FAU - Khrestchatisky, Michel AU - Khrestchatisky M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Glia JT - Glia JID - 8806785 RN - 0 (Lysosomal-Associated Membrane Protein 2) RN - 0 (Molecular Motor Proteins) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Active Transport, Cell Nucleus/physiology MH - Animals MH - Animals, Newborn MH - Astrocytes/*enzymology/ultrastructure MH - Cell Compartmentation/physiology MH - Cells, Cultured MH - Encephalitis/*enzymology/physiopathology MH - Gliosis/*enzymology/physiopathology MH - Lysosomal-Associated Membrane Protein 2/metabolism MH - Lysosomes/metabolism MH - Matrix Metalloproteinase 2/*metabolism MH - Matrix Metalloproteinase 9/*metabolism MH - Mice MH - Molecular Motor Proteins/metabolism MH - Protein Transport/physiology MH - Signal Transduction/physiology MH - Tissue Inhibitor of Metalloproteinase-1/metabolism MH - Tissue Inhibitor of Metalloproteinase-2/metabolism MH - Transport Vesicles/*enzymology/ultrastructure EDAT- 2009/09/26 06:00 MHDA- 2010/03/10 06:00 CRDT- 2009/09/26 06:00 PHST- 2009/09/26 06:00 [entrez] PHST- 2009/09/26 06:00 [pubmed] PHST- 2010/03/10 06:00 [medline] AID - 10.1002/glia.20927 [doi] PST - ppublish SO - Glia. 2010 Feb;58(3):344-66. doi: 10.1002/glia.20927.