PMID- 18817873 OWN - NLM STAT- MEDLINE DCOM- 20090130 LR - 20220317 IS - 1095-9327 (Electronic) IS - 1044-7431 (Linking) VI - 39 IP - 4 DP - 2008 Dec TI - Vesicular trafficking and secretion of matrix metalloproteinases-2, -9 and tissue inhibitor of metalloproteinases-1 in neuronal cells. PG - 549-68 LID - 10.1016/j.mcn.2008.08.004 [doi] AB - Matrix metalloproteinases (MMPs) are endopeptidases that cleave matrix, soluble and membrane-bound proteins and are regulated by their endogenous inhibitors the tissue inhibitors of MMPs (TIMPs). Nothing is known about MMP/TIMP trafficking and secretion in neuronal cells. We focussed our attention on the gelatinases MMP-2 and MMP-9, and their inhibitor TIMP-1. MMPs and TIMP-1 fused to GFP were expressed in N2a neuroblastoma and primary neuronal cells to study trafficking and secretion using real time video-microscopy, imaging, electron microscopy and biochemical approaches. We show that MMPs and TIMP-1 are secreted in 160-200 nm vesicles in a Golgi-dependent pathway. These vesicles distribute along microtubules and microfilaments, co-localise differentially with the molecular motors kinesin and myosin Va and undergo both anterograde and retrograde trafficking. MMP-9 retrograde transport involves the dynein/dynactin molecular motor. In hippocampal neurons, MMP-2 and MMP-9 vesicles are preferentially distributed in the somato-dendritic compartment and are found in dendritic spines. Non-transfected hippocampal neurons also demonstrate vesicular secretion of MMP-2 in both its pro- and active forms and gelatinolytic activity localised within dendritic spines. Our results show differential trafficking of MMP and TIMP-1-containing vesicles in neuronal cells and suggest that these vesicles could play a role in neuronal and synaptic plasticity. FAU - Sbai, Oualid AU - Sbai O AD - Neurobiologie des Interactions Cellulaires et Neurophysiopathologie (NICN), UMR 6184 CNRS-Universite de la Mediterranee, Faculte de Medecine, IFR Jean Roche, Bd Pierre Dramard, 13916 Marseille Cedex 20, France. FAU - Ferhat, Lotfi AU - Ferhat L FAU - Bernard, Anne AU - Bernard A FAU - Gueye, Yatma AU - Gueye Y FAU - Ould-Yahoui, Adlane AU - Ould-Yahoui A FAU - Thiolloy, Sophie AU - Thiolloy S FAU - Charrat, Eliane AU - Charrat E FAU - Charton, Gerard AU - Charton G FAU - Tremblay, Evelyne AU - Tremblay E FAU - Risso, Jean-Jacques AU - Risso JJ FAU - Chauvin, Jean-Paul AU - Chauvin JP FAU - Arsanto, Jean-Pierre AU - Arsanto JP 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 DEP - 20080904 PL - United States TA - Mol Cell Neurosci JT - Molecular and cellular neurosciences JID - 9100095 RN - 0 (Molecular Motor Proteins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Animals MH - Biological Transport/physiology MH - Cells, Cultured MH - Cytoplasmic Vesicles/*metabolism MH - Cytoskeleton/metabolism/ultrastructure MH - Humans MH - Matrix Metalloproteinase 2/genetics/*metabolism MH - Matrix Metalloproteinase 9/genetics/*metabolism MH - Mice MH - Molecular Motor Proteins/metabolism MH - Neurons/cytology/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Recombinant Fusion Proteins/genetics/*metabolism MH - Tissue Inhibitor of Metalloproteinase-1/genetics/*metabolism EDAT- 2008/09/27 09:00 MHDA- 2009/01/31 09:00 CRDT- 2008/09/27 09:00 PHST- 2008/05/01 00:00 [received] PHST- 2008/07/08 00:00 [revised] PHST- 2008/08/09 00:00 [accepted] PHST- 2008/09/27 09:00 [pubmed] PHST- 2009/01/31 09:00 [medline] PHST- 2008/09/27 09:00 [entrez] AID - S1044-7431(08)00219-4 [pii] AID - 10.1016/j.mcn.2008.08.004 [doi] PST - ppublish SO - Mol Cell Neurosci. 2008 Dec;39(4):549-68. doi: 10.1016/j.mcn.2008.08.004. Epub 2008 Sep 4.