Peter Penzes

..Finally, we discuss the importance of these actin regulatory pathways in neuropsychiatric disorders...

..We will place special emphasis on small GTPase pathways, as they have an established importance in dendritic spine plasticity and pathology. Finally, we will discuss some epigenetic mechanisms that control spine morphogenesis...

..Spine stabilizing pathways may thus represent efficacious therapeutic targets for combating AD pathology...

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..Here, we review recent studies that have genetically and functionally linked kalirin signaling to a number of human disorders. Kalirin signaling may thus represent a disease mechanism and provide a novel therapeutic target...

..Microtubules, long thought to be absent from dendritic spines, are capable of controlling spine morphology, opening up a new line of investigation into mechanisms of spine plasticity and maintenance...

..Through this pathway, CaMKs and RacGEFs amplify calcium signals and translate them into spatially and temporally regulated structural remodeling of dendritic spines...

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..Thus, we identify a previously unknown mechanism that promotes dynamic remodeling and depression of spiny synapses, disruption of which may contribute to some aspects of disease...

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..Collectively, these data suggest that afadin is required for the maintenance of dendritic structure and excitatory tone...

..This work describes a form of two-step wiring plasticity relevant for cortical memory and identifies targets that may facilitate recovery from brain injuries...

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..These data demonstrate important roles for kalirin in the regulation of cortical structure, ultrastructure, and spine structural plasticity...

..These studies allow the comparison of the phenotypes of different kalirin mutant mice and shed light on the brain region-specific functions of small GTPase signaling...

..Together, these findings provide novel insight into the molecular and cellular substrates of social and communication behavior...

..These results suggest a potential role for serotonin signaling in modulating spine morphology and kalirin-7's function at cortical synapses...

..These results implicate ERβ signaling in controlling dendritic spine morphology, in part via a PAK/ERK1/2-dependent pathway, and provide mechanistic insight into the rapid cellular effects of estrogen on brain function...

..These results demonstrate that extinction mechanisms based on Erk signaling involve a specific population of CA1 principal neurons distinctively regulated by afferent cholinergic input from the medial septum...

..Our data support spines as neuronal structures important for cognition and suggest interplay between brain regions is critical for complex cognitive processing...

..Overall, our findings indicate that kalirin-7 is differentially compartmentalized in spines as a function of both synapse morphology and spine size...

..Several of these deficits are delayed and age-dependent. Our study thus links spine morphogenic signaling with age-dependent, delayed, disease-related phenotypes, including cognitive dysfunction...

..Similar results were obtained in other tissue-invasive cells such as vascular endothelial cells, suggesting a novel mechanism for functional coupling of matrix adhesion with Wnt signaling...

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..The data suggest that the newly identified role of hippocampal N-cadherin in memory consolidation may be mediated, at least in part, by cytoskeletal IQGAP1/Erk signaling...

..These results identify a signaling pathway that regulates activity-dependent synaptic structural plasticity and coordinates it with functional plasticity...

..Together these data suggest that downregulation of CTGF in EOC cells may be important for cell invasion through modulation of cell-matrix adhesion...

..We will then go on to discuss the potential role of 17 β-estradiol modulation of neural circuits and its potential relevance for the treatment of psychiatric and neurodevelopmental disorders...

..This novel signal transduction pathway may be critical for the regulation of the actin cytoskeleton controlling spine morphogenesis during development and plasticity...

..serine/threonine phosphorylation, and generate initial information about the types of protein kinases involved. Together, these experiments will provide a basis for future studies of regulation of kalirin-7 and spine morphogenesis. ..

..These studies will use primary cultures of cortical and hippocampal neurons. ..

..As both spine density and kalirin expression are reduced in schizophrenic patients'brains, these studies are expected to provide important insight into the mechanisms of spine pathology in mental disorders. 1 ..