Interaction of TAG1 and CASPR2, Proteins Associated to Autism Disorder?

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects brain development, social and communication skills. Although the causes of the disease are mostly unknown rare variations of the CANTNAP2, the gene that codes for contactin‐associated protein‐like 2 (CASPR2), have been implicated in ASD. We compared the cellular localization and glycosylation processing of wild type CASPR2 to twelve CASPR2 point mutations found in autistic individuals. In contrast to the wild‐type protein that localizes to the cell surface, mutants showed altered cellular disposition with endoplasmic reticulum retention and activation of one signaling pathway of the unfolded protein response. As CASPR2 is associated with a set of neuropsychiatric diseases, it is of interest to study the interaction of CASPR2 with proteins such as the transient axonal glycoprotein‐1 (TAG1). We are currently studying the interaction between different CASPR2 mutants and TAG1 by various biochemical techniques. Preliminary results show that we can measure the interaction between wild‐type TAG1 and wild type CASPR2, but not with one CASPR2 mutants. This data suggest that the interaction is disrupted by the mutation but also that another protein could be mediating this interaction. These studies will help understand better the biology of CASPR2 and its specific role in the development of autism and other neurodevelopmental disorders.