RT Journal Article
T1 The brain-tumor related protein podoplanin regulates synaptic plasticity and hippocampus-dependent learning and memory.
A1 Cicvaric, Ana
A1 Yang, Jiaye
A1 Krieger, Sigurd
A1 Khan, Deeba
A1 Kim, Eun-Jung
A1 Dominguez-Rodriguez, Manuel
A1 Cabatic, Maureen
A1 Molz, Barbara
A1 Acevedo Aguilar, Juan Pablo
A1 Milicevic, Radoslav
A1 Smani, Tarik
A1 Breuss, Johannes M
A1 Kerjaschki, Dontscho
A1 Pollak, Daniela D
A1 Uhrin, Pavel
A1 Monje, Francisco J
K1 Ezrin
K1 Podoplanin
K1 dentate gyrus
K1 hippocampus
K1 memory
K1 nerve growth factor
K1 neuron
K1 synaptic plasticity
AB 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.
YR 2016
FD 2016-08-25
LK http://hdl.handle.net/10668/10390
UL http://hdl.handle.net/10668/10390
LA en
DS RISalud
RD Apr 9, 2025