SynCAM 1 participates in axo-dendritic contact assembly and shapes neuronal growth cones

Abstract

Neuronal growth cones are highly motile structures that tip developing neurites and explore their surroundings before axo-dendritic contact and synaptogenesis. However, the membrane proteins organizing these processes remain insufficiently understood. Here we identify that the synaptic cell adhesion molecule 1 (SynCAM 1), an immunoglobulin superfamily member, is already expressed in developing neurons and localizes to their growth cones. Upon interaction of growth cones with target neurites, SynCAM 1 rapidly assembles at these contacts to form stable adhesive clusters. Synaptic markers can also be detected at these sites. Addressing the functions of SynCAM 1 in growth cones preceding contact, we determine that it is required and sufficient to restrict the number of active filopodia. Further, SynCAM 1 negatively regulates the morphological complexity of migrating growth cones. Focal adhesion kinase, a binding partner of SynCAM 1, is implicated in its morphogenetic activities. These results reveal that SynCAM 1 acts in developing neurons to shape migrating growth cones and contributes to the adhesive differentiation of their axo-dendritic contacts.

SynCAMs – From axon guidance to neurodevelopmental disorders

“…The role of SynCAM1 and SynCAM2 in synaptogenesis has been extensively studied, as this feature was the basis for their discovery (Fogel et al, 2007;Stagi et al, 2010;Robbins et al, 2010;Park et al, 2016). Confirmation of the role of SynCAMs in synapse formation came from heterologous co-culture assays (Biederer and Scheiffele, 2007;see above) showing that overexpression of SynCAM1 in non-neuronal cells induced functional presynaptic terminal differentiation in cocultured hippocampal neurons (Biederer et al, 2002;Sara et al, 2005).…”

Micropatterned substrates coated with neuronal adhesion molecules for high-content study of synapse formation

“…To examine whether our system could be used to induce presynapses using synaptogenic proteins other than Nlg1, we cultured neurons on micropatterned substrates coated with SynCAM1, an adhesion molecule involved in axonal growth and synaptic differentiation 20,22,24 (Fig. 5a,b).…”

“…Besides Nrxs and Nlgs, SynCAMs represent another family of synaptic organizers. SynCAMs are immunoglobulin cell adhesion molecules that are able to form both homophilic and heterophilic interactions, and connect intracellularly with PDZ and FERM domain-containing proteins [20][21][22][23][24] . The ability of SynCAMs to trigger synaptic specialization was demonstrated using both knock-out mice and cell culture assays [20][21][22][23][24] .…”

Polysialylation of the Synaptic Cell Adhesion Molecule 1 (SynCAM 1) Depends Exclusively on the Polysialyltransferase ST8SiaII in Vivo

“…SynCAM 1 is prominently expressed in the developing and mature brain, mediating Ca 2ϩ -independent homo-and heterophilic interactions across the nascent and mature synaptic cleft (1)(2)(3). In developing neurons, SynCAM 1 shapes migrating growth cones, assembles at axo-dendritic contacts, and participates in adhesive trans interactions that induce presynaptic specializations (4,5). Moreover, studies on genetic mouse models with increased or no SynCAM 1 expression demonstrated a crucial role of this synapse-organizing molecule in regulating the number and plasticity of excitatory synapses (6).…”