Neuronal Ig/Caspr Recognition Promotes the Formation of Axoaxonic Synapses in Mouse Spinal Cord

Abstract

SummaryInhibitory microcircuits are wired with a precision that underlies their complex regulatory roles in neural information processing. In the spinal cord, one specialized class of GABAergic interneurons (GABApre) mediates presynaptic inhibitory control of sensory-motor synapses. The synaptic targeting of these GABAergic neurons exhibits an absolute dependence on proprioceptive sensory terminals, yet the molecular underpinnings of this specialized axoaxonic organization remain unclear. Here, we show that sensory expression of an NB2 (Contactin5)/Caspr4 coreceptor complex, together with spinal interneuron expression of NrCAM/CHL1, directs the high-density accumulation of GABAergic boutons on sensory terminals. Moreover, genetic elimination of NB2 results in a disproportionate stripping of inhibitory boutons from high-density GABApre-sensory synapses, suggesting that the preterminal axons of GABApre neurons compete for access to individual sensory terminals. Our findings define a recognition complex that contributes to the assembly and organization of a specialized GABAergic microcircuit.

Structural Basis for Interactions Between Contactin Family Members and Protein-tyrosine Phosphatase Receptor Type G in Neural Tissues

“…Such a possibility would be consistent with our results showing that PTPRG binds to CNTN3-6 in essentially identical fashion. These PTPRG⅐CNTN co-receptors might associate with known CNTN-binding partners, such as L1 family members, CNTNAPs, or amyloid precursor proteins (8,11,32,34,35). Targets of PTPRG⅐CNTN co-receptor complexes might also include yet to be identified proteins that have weak affinities for either PTPRG or a given CNTN but would associate with a PTPRG⅐CNTN co-receptor complex to form a holoreceptor in much the same way that semaphorins, neuropilins, and plexins do (36).…”

Making the connection – shared molecular machinery and evolutionary links underlie the formation and plasticity of occluding junctions and synapses

“…The calyceal synapses of vestibular hair cells in the mouse show a high similarity to septate junctions in EM microscopy and contain both Caspr and contactin, with loss of Caspr resulting in the separation of the membranes at the synapse (Lysakowski et al, 2011;Sousa et al, 2009). Recently, it has been demonstrated that a contactin5 (CNTN5)-Caspr4 complex together with the IgCAM NgCAM-related cell adhesion molecule (NrCAM) guides the formation of synapse-to-synapse (axoaxonic) synapses between GABAergic interneurons and sensory motor synapses in the spinal cord, and there are likely to be other examples of 'transitional' synapses that would benefit from further molecular characterization (Ashrafi et al, 2014).…”

Morphophysiological alterations caused by insertional mutagenesis of contactin 5 (Cntn5) gene in transgenic mice

“…Характерной чертой контактинов является большой размер -порядка 1.2 M bp в случае Cntn5. Всего описано шесть схожих по структуре генов контактинов, которые экспрессируются в основном в нейронах головного (Kleijer et al, 2015) и спинного мозга (Ashrafi et al, 2014) и регулируют образование синапсов между нейронами, обеспечивая различные аспекты нерв-ной деятельности. Контактин-5 экспрессируется главным образом в центральной нервной системе (Ogawa et al, 1996), а его максимальная экспрессия обнаруживается у эмбрионов мышей начиная с 16-го дня и на 2-й день после рождения (Li et al, 2003).…”