Contactins: emerging key roles in the development and function of the nervous system

Abstract

Contactins are a subgroup of molecules belonging to the immunoglobulin superfamily that are expressed exclusively in the nervous system. The subgroup consists of six members: contactin, TAG-1, BIG-1, BIG-2, NB-2 and NB-3. Since their identification in the late 1980s, contactin and TAG-1 have been studied extensively. Axonal expression and the neurite extension activity of contactin and TAG-1 attracted researchers to study the function of these molecules in axon guidance during development. After the exciting discovery of the molecular function of contactin and TAG-1 in myelination earlier this decade, these two molecules have come to be known as the principal molecules in the function and maintenance of myelinated neurons. In contrast, the function of the other four members of this subgroup remained unknown until recently. Here, we will give an overview of contactin function, including recent progress on BIG-2, NB-2 and NB-3.

Figures

Figure 1

Contactins consist of six immunoglobulin-like domains and four fibronectin type III-like domains that are linked to the plasma membrane through a GPI-anchor.

Figure 2

The interactions of contactins in a variety of tissues/cells/compartments. Contactins are drawn in blue, and other molecules are in green. (A) The molecular complexes in the myelinated nerves. (B) Interactions of contactins with molecules of the L1 family and NCAM. (C) Interactions of contactins with PTPα. (D) Interactions of contactins with Notch and molecules of the APP family.