SynCAM 1 participates in axo-dendritic contact assembly and shapes neuronal growth cones.
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.
Stagi
Massimiliano
M
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Fogel
Adam I
AI
Biederer
Thomas
T
D000818:Animals; D001369:Axons / Q000378:metabolism*; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002465:Cell Movement; D003712:Dendrites / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007136:Immunoglobulins / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
C498598:Cadm1 protein, mouse; C465040:Cadm1 protein, rat; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D007136:Immunoglobulins; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins