THE LEUCINE-RICH REPEAT TRANSMEMBRANE PROTEIN LRIG1 RESTRICTS HIPPOCAMPAL DENDRITE COMPLEXITY BY MODULATING NEUROTROPHIN-INDUCED TRKB SIGNALING

CRUZ ALSINA, F; HITA, F; FONTANET, P; IRALA, D; LEDDA, F; PARATCHA, G

Simposio; Joint ASBMB/IUBMB SISTAM 2015 Meeting; 2015

SISTAM 2015

Dendrite size and morphology are key determinants of the functional properties of neurons, and many neurodevelopmental and psychiatric disorders are due primarily to structural abnormalities of dendrites and their connections. Dendritic development results from the interaction between extracellular signals, intrinsic modulators and electrical activity. Compared with the many identified factors that promote general dendritic growth and branching, little is known about the cell-type specific modulators that allow neurons to sculpt distinctive dendrite patterns. Here, we show that leucine-rich repeats and immunoglobulin-like domains-1 (Lrig1) is a physiological inhibitor of hippocampal dendrite morphogenesis and branching. Knockdown of Lrig1 enhances both primary dendrite formation and proximal dendritic branching, two phenotypes that resemble the effect of BDNF on hippocampal neurons. Our results show that Lrig1 interacts with TrkB and inhibits BDNF/TrkB signaling associated to dendrite development. Lrig1-deficient hippocampal neurons display an enhanced proximal dendritic arborization and TrkB activation in response to BDNF. Together, our findings reveal that Lrig1 regulates hippocampal dendrite development through the inhibition of BDNF/TrkB signaling and suggest that Lrig1 controls the patterns of dendritic morphology by increasing the repertoire of TrkB signaling outputs.