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Title: The brain-tumor related protein podoplanin regulates synaptic plasticity and hippocampus-dependent learning and memory.
Authors: Cicvaric, Ana
Yang, Jiaye
Krieger, Sigurd
Khan, Deeba
Kim, Eun-Jung
Dominguez-Rodriguez, Manuel
Cabatic, Maureen
Molz, Barbara
Acevedo Aguilar, Juan Pablo
Milicevic, Radoslav
Smani, Tarik
Breuss, Johannes M
Kerjaschki, Dontscho
Pollak, Daniela D
Uhrin, Pavel
Monje, Francisco J
Keywords: Ezrin;Podoplanin;dentate gyrus;hippocampus;memory;nerve growth factor;neuron;synaptic plasticity
metadata.dc.subject.mesh: Animals
Gene Knockout Techniques
Membrane Glycoproteins
Neuronal Plasticity
Issue Date: 25-Aug-2016
Abstract: Podoplanin is a cell-surface glycoprotein constitutively expressed in the brain and implicated in human brain tumorigenesis. The intrinsic function of podoplanin in brain neurons remains however uncharacterized. Using an established podoplanin-knockout mouse model and electrophysiological, biochemical, and behavioral approaches, we investigated the brain neuronal role of podoplanin. Ex-vivo electrophysiology showed that podoplanin deletion impairs dentate gyrus synaptic strengthening. In vivo, podoplanin deletion selectively impaired hippocampus-dependent spatial learning and memory without affecting amygdala-dependent cued fear conditioning. In vitro, neuronal overexpression of podoplanin promoted synaptic activity and neuritic outgrowth whereas podoplanin-deficient neurons exhibited stunted outgrowth and lower levels of p-Ezrin, TrkA, and CREB in response to nerve growth factor (NGF). Surface Plasmon Resonance data further indicated a physical interaction between podoplanin and NGF. This work proposes podoplanin as a novel component of the neuronal machinery underlying neuritogenesis, synaptic plasticity, and hippocampus-dependent memory functions. The existence of a relevant cross-talk between podoplanin and the NGF/TrkA signaling pathway is also for the first time proposed here, thus providing a novel molecular complex as a target for future multidisciplinary studies of the brain function in the physiology and the pathology. Key messages Podoplanin, a protein linked to the promotion of human brain tumors, is required in vivo for proper hippocampus-dependent learning and memory functions. Deletion of podoplanin selectively impairs activity-dependent synaptic strengthening at the neurogenic dentate-gyrus and hampers neuritogenesis and phospho Ezrin, TrkA and CREB protein levels upon NGF stimulation. Surface plasmon resonance data indicates a physical interaction between podoplanin and NGF. On these grounds, a relevant cross-talk between podoplanin and NGF as well as a role for podoplanin in plasticity-related brain neuronal functions is here proposed.
metadata.dc.identifier.doi: 10.1080/07853890.2016.1219455
Appears in Collections:Producción 2020

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