%0 Journal Article
%A Cicvaric, Ana
%A Yang, Jiaye
%A Krieger, Sigurd
%A Khan, Deeba
%A Kim, Eun-Jung
%A Dominguez-Rodriguez, Manuel
%A Cabatic, Maureen
%A Molz, Barbara
%A Acevedo Aguilar, Juan Pablo
%A Milicevic, Radoslav
%A Smani, Tarik
%A Breuss, Johannes M
%A Kerjaschki, Dontscho
%A Pollak, Daniela D
%A Uhrin, Pavel
%A Monje, Francisco J
%T The brain-tumor related protein podoplanin regulates synaptic plasticity and hippocampus-dependent learning and memory.
%D 2016
%U http://hdl.handle.net/10668/10390
%X 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.
%K Ezrin
%K Podoplanin
%K dentate gyrus
%K hippocampus
%K memory
%K nerve growth factor
%K neuron
%K synaptic plasticity
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