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The unique functions and morphology of neurons require a specialized endosomal system that recycles, sorts, and targets proteins. The neuronal endosome is unique in that it is polarized into somatodendritic and axonal domains, has neuronal-specifi c regulators, and is modulated by generic regulators that confer neuronal-specifi c properties. NEEP21, a neuronal-specifi c early endosomal regulator, and EEA1, a generic early endosomal regulator, are polarized to somatodendritic domain and bind syntaxin13 (stx13), which occupies early/recycling endosomes in somatodendritic and axonal domains. NEEP21 and stx13 regulate AMPA receptor recycling; NEEP21 regulates traffi cking of L1 cell adhesion molecule. It is not known how these endosomal regulators function together to transport cargo in neurons. Due to the dynamic nature of the endosomal system, live imaging is required to understand the relationships and dynamics of different compartments. We carried out live imaging of GFP/RFPtagged regulators in cultured hippocampal neurons. NEEP21 occupies stationary (containing L1) and dynamic (devoid of L1) round compartments. EEA1-containing round and static compartments do not signifi cantly colocalize with NEEP21, but often are adjacent to it. Stx13 resides in dynamic, elongated carriers and in round stationary compartments where it partially colocalizes with EEA1 and NEEP21. We interfered with function of stx13 using expression of dominantnegative construct and found that it affects L1 traffi cking.
Matrix metalloproteinases (MMPs) are considered to play a pivotal role in remodeling of the extracellular matrix in health and disease. Recent studies suggest that MMP-9 plays an important role in synaptic plasticity, learning and memory. It was shown that MMP-9 occurs in postsynaptic part of hippocampal synapses, where the amount and activity of MMP-9 were increased by stimulation leading plasticity changes. At the neuromuscular junction, a role, related to the turnover of agrin, has been demonstrated for MMP-3. Although MMP-9 has been localized to NMJ, neither its role nor precise distribution in relation to synaptic elements is established unequivocally. Here, we have carried out the investigation of the gelatinolytic activity of NMJ in rats, in order to establish whether high-intensity exercise can promote expression of MMP-9 at the NMJ. Our fi nding of the present work is that training increases the gelatinolytic activity of the NMJ in the extensor digitorium longus and soleus muscles. The 4-week endurance training program elicited alterations at the presynaptic side of the NMJ, where the increasing gelatinolytic activity was localized in the Schwann cells. These data shows that endurance training infl uences on the gelatinolytic activity of NMJ, possibly through synaptic transmission.
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