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TIMP, synapse

Jarrod Shilts, Kendal Broadie
Synaptogenesis is coordinated by trans -synaptic signals that traverse the specialized synaptomatrix between presynaptic and postsynaptic cells. Matrix metalloproteinase (Mmp) activity sculpts this environment, balanced by secreted tissue inhibitors of Mmp (Timp). Here, we use the simplified Drosophila melanogaster matrix metalloproteome to test the consequences of eliminating all Timp regulatory control of Mmp activity at the neuromuscular junction (NMJ). Using in situ zymography, we find Timp limits Mmp activity at the NMJ terminal and shapes extracellular proteolytic dynamics surrounding individual synaptic boutons...
July 15, 2017: Journal of Cell Science
Marta Magnowska, Tomasz Gorkiewicz, Anna Suska, Marcin Wawrzyniak, Izabela Rutkowska-Wlodarczyk, Leszek Kaczmarek, Jakub Wlodarczyk
Activity-dependent proteolysis at a synapse has been recognized as a pivotal factor in controlling dynamic changes in dendritic spine shape and function; however, excessive proteolytic activity is detrimental to the cells. The exact mechanism of control of these seemingly contradictory outcomes of protease activity remains unknown. Here, we reveal that dendritic spine maturation is strictly controlled by the proteolytic activity, and its inhibition by the endogenous inhibitor (Tissue inhibitor of matrix metalloproteinases-1 - TIMP-1)...
2016: Scientific Reports
Ewelina Knapska, Victoria Lioudyno, Anna Kiryk, Marta Mikosz, Tomasz Górkiewicz, Piotr Michaluk, Maciej Gawlak, Mayank Chaturvedi, Gabriela Mochol, Marcin Balcerzyk, Daniel K Wojcik, Grzegorz M Wilczynski, Leszek Kaczmarek
Learning how to avoid danger and pursue reward depends on negative emotions motivating aversive learning and positive emotions motivating appetitive learning. The amygdala is a key component of the brain emotional system; however, an understanding of how various emotions are differentially processed in the amygdala has yet to be achieved. We report that matrix metalloproteinase-9 (MMP-9, extracellularly operating enzyme) in the central nucleus of the amygdala (CeA) is crucial for appetitive, but not for aversive, learning in mice...
September 4, 2013: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Saul S Siller, Kendal Broadie
Fragile X syndrome (FXS), caused by loss of the fragile X mental retardation 1 (FMR1) product (FMRP), is the most common cause of inherited intellectual disability and autism spectrum disorders. FXS patients suffer multiple behavioral symptoms, including hyperactivity, disrupted circadian cycles, and learning and memory deficits. Recently, a study in the mouse FXS model showed that the tetracycline derivative minocycline effectively remediates the disease state via a proposed matrix metalloproteinase (MMP) inhibition mechanism...
September 2011: Disease Models & Mechanisms
Santiago Rivera, Michel Khrestchatisky, Leszek Kaczmarek, Gary A Rosenberg, Diane M Jaworski
Members of the metzincin family of metalloproteinases have long been considered merely degradative enzymes for extracellular matrix molecules. Recently, however, there has been growing appreciation for these proteinases and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs), as fine modulators of nervous system physiology and pathology. Present all along the phylogenetic tree, in all neural cell types, from the nucleus to the synapse and in the extracellular space, metalloproteinases exhibit a complex spatiotemporal profile of expression in the nervous parenchyma and at the neurovascular interface...
November 17, 2010: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Lucia Leone, M Egle De Stefano, Arianna Del Signore, Tamara C Petrucci, Paola Paggi
We have previously shown that intraganglionic synapse disassembly consequent on superior cervical ganglion (SCG) neuron axotomy was preceded by the loss of the dystroglycan beta subunit (beta-DG) localized at the postsynaptic specializations. Because DG, a transmembrane molecular complex bridging the extracellular matrix to the cortical cytoskeleton, could be a physiological target of metalloproteinases (MMPs) 2 and 9, we investigated their possible involvement in the injury-induced intraganglionic synapse disassembly...
November 2005: Journal of Neuropathology and Experimental Neurology
Peng Yang, K Adam Baker, Theo Hagg
We have reported that alpha6beta1 integrin regulates the directed migration of neuroblasts from the adult rodent subventricular zone (SVZ) through the rostral migratory stream (RMS). ADAM (a disintegrin and metalloprotease) proteins bind integrins. Here, we show that ADAM21, but not ADAM2, -3, -9, -10, -12, -15, or -17, is expressed in adult rats and mice by ependyma and SVZ cells with long basal processes, and in radial glia at early postnatal times. ADAM21-positive processes projected into the RMS, contacted blood vessels, and were present within the RMS intermingled with neuroblasts up to where neuroblasts start their radial migration and differentiation in the olfactory bulb...
September 19, 2005: Journal of Comparative Neurology
C Vaillant, M Didier-Bazès, A Hutter, M F Belin, N Thomasset
Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade the components of the extracellular matrix (ECM). The balance between MMPs and their inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] in the pericellular environment determines the most significant proteolytic events in tissue remodeling. In vitro evidence is accumulating that these molecules may be crucial in the maturation of neural cells. Here, we investigated the in vivo expression of MMPs 2, 3, and 9 and TIMPs 1, 2, and 3 in the developing and adult rat cerebellum using immunohistochemistry and in situ hybridization...
June 15, 1999: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
L C Timpe, A E Stuart
The hypothesis that gamma-aminobutyric acid (GABA) is the neurotransmitter of barnacle photoreceptors was tested by studying the effect of GABA on the membrane of the cell directly postsynaptic to the photoreceptor, by testing the ability of GABA antagonists to block transmission at this synapse, and by estimating the free GABA content of the photoreceptor. The results of these experiments suggest that GABA is not the photoreceptor's neurotransmitter.
July 30, 1984: Brain Research
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