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INTRODUCTION: The Amot‑Yap1 complex plays a major role in the regulation of cell contact inhibition, cellular polarity and growth in many cell types. However, the function of the Amot and Hippo pathway transcription co‑activator Yap1 in the CNS remains unclear. Recent studies have demonstrated that, in mature hippocampal neurons, Amot localizes to dendritic spines where it associates with synaptic...
Arc protein was shown to control synaptic AMPA receptor content, dendritic spine maintenance, and structure. Given its importance for neuronal function, Arc protein expression has to be tightly regulated and it occurs via ubiquitination and proteasomal degradation. Glycogen synthase kinases α and β (GSK3α/β) are serine‑threonine kinases abundantly expressed in neuronal cells, crucial for neuronal...
INTRODUCTION: The mammalian target of rapamycin (mTOR) has an important role in the maturation of developing neuronal cells. It can be seen in the condition of mTOR hyper-activation, which leads to premature differentiation, uncontrolled overgrowth of the dendritic tree, and elevated cell soma sizes in in vitro cultures. In patients, this phenotype leads to diseases like tuberous sclerosis complex,...
The development of molecular biology methods in the early 1980s led to a better understanding of the role of transcription factors in mammalian cells. The discovery that some transcription factors are critically important for cells to switch between different functional states was fundamental for modern molecular neurobiology. In the 1980s Leszek Kaczmarek proposed that, analogically to the cell cycle...
INTRODUCTION: The mechanistic target of rapamycin (mTOR) is a protein kinase, which integrates eukaryotic cell growth, metabolism and external stimuli. Most research link mTOR with control of protein translation but recent studies revealed additional mTOR function in cell nucleus. Previously, we showed that phosphorylation of mTOR (Ser2448; P-mTOR) is upregulated in neuronal nucleus upon kainate (KA)...
INTRODUCTION: The proper dendritic branching is a highly regulated process. Among its regulators are membrane proteins internalized via clathrin-mediated endocytosis. AP2 adaptor complex is a key player in this process, but its role in mammalian dendritogenesis has not yet been tested. AIM(S): The aim of this study was to find how AP2 complex contributes to shaping dendritic tree of developing hippocampal...
INTRODUCTION: Rab11a is a protein that belongs to the small GTPase superfamily. It is known to be involved in the endocytic recycling. In neurons, it was demonstrated to participate in TrkB receptor translocation to the postsynaptic density in the chemical long-term potentiation (c-LTP) upon BDNF stimulation and in AMPA receptor recycling. Recycling endosomes were also shown to contribute to early...
Introduction: Mammalian target of rapamycin (mTOR) is a protein kinase that regulates cellular metabolism. Adequate mTOR activity is needed for development as well as proper physiology of mature neurons. Changes in mTOR activity are often observed in neuropathology. Several groups reported that seizures increase mTOR activity, and mTOR contributes to spontaneous seizures. However, the current knowledge...
BACKGROUND AND AIMS: Proper organization of synaptic connections is important for the transmission of information in the central and peripheral nervous systems (CNS and PNS). Synaptic remodeling is a process whereby synapses are rewired to form functional neuronal networks. The molecular mechanisms underlying this process are still poorly understood. We have recently identified the scaffold protein...
BACKGROUND AND AIMS: The proper functioning of neurons is defined by many different aspects such as dendritic branching and receptor composition within synapses. Abnormalities in dendritic tree development lead to serious dysfunctions of the nervous system. Not surprisingly, the multi-step process of dendritic tree development is highly regulated. In shRNA library screen we have identified several...
Mammalian target of rapamycin (mTOR) is a protein kinase that senses nutrient availability, trophic factors support, cellular energy level, cellular stress, neurotransmitters and adjusts cellular metabolism accordingly. Recently, several groups reported that seizures increase mTOR activity, and such increased activity in genetic models can contribute to spontaneous seizures. However, the current knowledge...
Dendrites are the main site of information input into neurons. Development of a dendritic tree is multistep and very complex process, which is tightly regulated by combination of extracellular cues and execution of intrinsic genetic program. An important cellular process for proper dendritic arbor development is local production of key structural proteins in response to neuronal activity and trophic...
GSK3 alpha/beta (Glycogen Synthase Kinases alpha/beta) are serine/threonine kinases ubiquitously expressed in the nervous system. GSK3’s appear to be critical for LTD formation and overactivation of GSK3 inhibits LTP expression. Here we report that GSK3 regulate expression of Arc/Arg3.1 protein (Activity Regulated Cytoskeleton Associated Protein/Activity Regulated Gene 3.1), involved in diverse forms...
CD44 is a widely distributed type I transmembrane glycoprotein and functions as the major hyaluronan receptor on most cell types. CD44 through interaction with actin cytoskeleton affects the transmission of signals from the outside to the inside of the cell in many tissues and organs. Primary cultures of astrocyte are diverse in their morphology and many factors can influence on it. In vivo astrocyte...
Zipcode Binding Protein 1 (ZBP1) is one of proteins involved in local translation, a mechanism present in various cell types. In neurons,processes coordinated by ZBP1 are indispensable for proper axonal growth cone and spine formation, as well as dendritic arborization. Recently we also showed that ZBP1-dependent dendritic transport of b-actin mRNA and its local translation is needed for dendritic...
Dendritic arborization patterns define neuronal subtypes, and have important functional implications, determining how signals coming from individual synapses are integrated. Developing dendrites of neurons are responsive to extrinsic signals. Although several secreted proteins, cell surface receptors and adhesion molecules have been recently shown to be involved in dendrite morphogenesis, the role...
Immediate-early genes, c-fos in particular, are expressed in the brain upon neuronal activation. c-Fos expression is thought to reflect novelty detection and propensity for a plastic change as its levels decrease when the animal fully acquire a new task. However, its functional role in the brain remains largely unknown. In the present study, we used c-Fos immmunolabeling to identify the cortical network...
MMP-9 is an endopeptidase playing important role in neuronal plasticity. Although multiple factors regulating MMP-9 expression have been described in different cell types, the molecular mechanism directly controlling its transcription in neurons remains poorly understood. The aim of the current study was to determine, whether SRF/c-Fos pathway is involved in the transcriptional regulation of MMP-9...
The common effects of epileptic seizures are aberrant plastic changes in synaptic connectivity and morphological rearrangements in hippocampal mossy fi bers. This phenomenon is believed to be a basis of facilitation of further epileptic episodes, however its molecular mechanism remains elusive. mTOR kinase is crucial for rearrangements of neuronal morphology and for long term synaptic plasticity....
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