Assembly of neuronal connectivity by neurotrophic factors and leucine-rich repeat transmembrane proteins

PARATCHA GUSTAVO

Mar Del Plata

Congreso; reunion anual SAIC-SAF-SAFIS; 2018

SAIC-SAI-SAFIS

Proper function of the nervous system critically relies on sophisticated neuronal networks interconnected in a highly specific pattern. The architecture of these connections arises from sequential developmental steps such as axonal growth and guidance, dendrite development, target determination, synapse formation and plasticity. Leucine-rich repeat (LRR) transmembrane proteins have been directly linked to different human brain disorders, including autism, schizophrenia, obsessive-compulsive disorders, epilepsy, essential tremor, Alzheimer and Parkinson´s disease. The members of this superfamily of proteins execute their functions acting as trans-synaptic cell adhesion molecules involved in target specificity and synapse formation or working in cis as cell-intrinsic modulators of neurotrophic factor receptor trafficking and signaling. Here, we present a novel physiological contribution of the LRR transmebrane protein Lrig1 as an endogenous inhibitor of hippocampal dendrite morphogenesis and branching. Our data establish that Lrig1 is an essential molecule linking TrkB signaling to dendrite development and suggest that Lrig1 contributes to shape distinctive patterns of dendritic arborization in specific neuronal populations in response to neurotrophins. Furthermore, loss of Lrig1 led not only to morphological abnormalities, but also to social interaction deficits, highlighting the importance of this cell-intrinsic modulator for normal nervous system development and plasticity. Because several neuropsychiatric disorders are associated with altered dendrite morphology and social phenotypes, our findings raise the possibility that Lrig1 dysfunction may contribute to different neurological disorders.