Abstract
Immunoglobulin superfamily (IgSF) cell adhesion molecules (CAMs) are cell surface glycoproteins that not only mediate interactions between neurons but also between neurons and other cells in the nervous system. While typical IgSF CAMs are transmembrane molecules, this superfamily also includes CAMs, which do not possess transmembrane and intracellular domains and are instead attached to the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor. In this review, we focus on the role GPI-anchored IgSF CAMs have as signal transducers and ligands in neurons, and discuss their functions in regulation of neuronal development, synapse formation, synaptic plasticity, learning, and behavior. We also review the links between GPI-anchored IgSF CAMs and brain disorders.
Highlights
Cell adhesion molecules (CAMs) are expressed across all cell types
Further research is needed to characterize the whole repertoire of the interactions of GPI-anchored Immunoglobulin superfamily (IgSF) cell adhesion molecules (CAMs) in developing and mature neurons, and in synapses to fully understand the role these molecules play in the developing and mature nervous system and molecular mechanisms involved
It is possible that GPIanchored IgSF CAMs promote synapse formation by forming homophilic adhesive bonds connecting pre- and post-synaptic membranes
Summary
Cell adhesion molecules (CAMs) are expressed across all cell types. In the nervous system, multiple families of CAMs are expressed in neurons, including integrins, cadherins, selectins, neuroligins, neurexins, and the immunoglobulin superfamily (IgSF) of CAMs (Brümmendorf and Rathjen, 1993; Chothia and Jones, 1997; Buckley et al, 1998; Südhof, 2008; Sytnyk et al, 2017). In the human and murine genomes, genes coding for GPI-anchored IgSF CAMs include NEGR1, opioid-binding cell adhesion molecule (OBCAM), neurotrimin (Ntm), limbic systemassociated membrane protein (LAMP), IgLON5, contactin-1, -2, -3, -4, -5, -6, Thy-1, and carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-5, -6, -7, and -8 (Williams and Gagnon, 1982; Oikawa et al, 1987; Yoshihara et al, 1994, 1995; Hachisuka et al, 1996; Ogawa et al, 1996; Funatsu et al, 1999; Itoh et al, 2008; Sabater et al, 2016) (Table 1 and Figure 1). In addition to mediating trans-interactions, IgSF CAMs bind in cis, i.e., laterally, to surface proteins present in the same cell surface plasma membrane (Held and Mariuzza, 2011). In wild-type mice, the parallel fibers of granule cells extend perpendicular to the Frontiers in Molecular Neuroscience | www.frontiersin.org
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