027 | The glycoprotein GPM6a and the adhesion molecule ICAM5 enhance neuronal plasticity

Cellular and Molecular Neurobiology

Author: Rocio Gutierrez Fuster | Email: rgutierrezfuster@iib.unsam.edu.ar

Rocio Gutiérrez Fuster , Antonella León , Gabriela Inés Aparicio , Facundo Brizuela , Valentina Farias , Camila Scorticati

1° Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM) – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , San Martín, Buenos Aires, Argentina.
2° Department of Neurosurgery, College of Medicine, University of Kentucky, Lexington, USA.

The molecular mechanisms of neuronal structural plasticity are not fully understood. In this regards, neuronal membrane glycoprotein M6a promotes neuronal plasticity through unclear mechanisms. Since the extracellular loops of GPM6a (ECs) command its function, previous results from our laboratory determined that the intercellular cellular adhesion molecule 5, ICAM5, co-immunoprecipitated with the ECs of GPM6a. Here, we aimed to study the possible functional association of GPM6a and ICAM5 in hippocampal culture neurons and cell lines. We found that ICAM5 colocalized in cis with GPM6a in neurons at 5 DIV and N2a cells. Moreover, hippocampal neurons and N2a cells co-expressing GPM6a/ICAM5 showed significantly higher filopodia number and neurite extension compared to neurons and N2a cells overexpressing GPM6a or ICAM5 alone. Moreover, ICAM5 rescued GPM6a-ECs mutant´s phenotype when both protein were coexpressed in neurons and N2a cells. Cell aggregation assays were performed in order to validate extracellular domains interaction between ICAM5-ectodomain and GPM6a-ECs in HEK293 cells. We found at 20 minutes a significant increase in double aggregates of GPM6a cells with ICAM5 cells compared to the control groups and GPM6a mutant. Taken together, we validate the association between GPM6a and ICAM5 probably through their extracellular domains. Furthermore, both proteins induce neuronal structural plasticity synergistically.