022 | Tetraspanin 8 as a regulator of hippocampal dendrite development and connectivity

Cellular and Molecular Neurobiology

Author: Micaela Daiana Garcia | Email: mdgarcia@fmed.uba.ar

Micaela Daiana Garcia , Fernanda Ledda , Gustavo Paratcha

1° Instituto de Biología Celular y Neurociencias (IBCN)-CONICET-UBA, Facultad de Medicina, Universidad de Buenos Aires
2° Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA)-CONICET, Fundación Instituto Leloir

During nervous system development, the formation of neuronal connectivity requires the precise control of dendrite growth, branching and synapse formation. Tetraspanins (TSPANs) represent a large family of proteins that participate in the control of neuronal development. Despite the progress obtained in recent years, little is known about the role of TSPAN8 in the control of hippocampal dendrite development and synaptic connectivity. Here, we observed that TSPAN8 is expressed in the rat hippocampus during the first two weeks of postnatal development and into adulthood. Immunofluorescence assays show that TSPAN8 is localized in the CA1-CA3 regions and dentate gyrus of the developing mouse hippocampus. By using subcellular fractionation, we also observed that TSPAN8 is present in hippocampal synaptic fractions, including the postsynaptic density. Taking advantage of the postnatal expression of TSPAN8 by hippocampal developing neurons, we used loss of function assays to examine how altered TSPAN8 expression impacts dendrite morphology and dendritic spine formation and maturation of these neurons. Our findings demonstrate that TSPAN8 regulates dendrite growth, branching and complexity of hippocampal neurons. Loss-of-function assays also show that reduced TSPAN8 levels cause a significant increase in the density of hippocampal dendritic spines, thus suggesting that TSPAN8 might regulate the formation of excitatory synaptic contacts of developing hippocampal neurons.