N-cadherin-dependent neuron–neuron interaction is required for the maintenance of activity-induced dendrite growth

Abstract

Formation of neural circuits depends on stable contacts between neuronal processes, mediated by interaction of cell adhesion molecules, including N-cadherin. In the present study, we found that activity-dependent dendrite arborization specifically requires Ncadherin-mediated extracellular neuron-neuron interaction, because the enhancement did not occur for neurons cultured in isolation or plated on an astrocyte monolayer and was abolished by a recombinant soluble N-cadherin ectodomain. Furthermore, depolarization elevated the level of membrane-associated cadherin/catenin complexes and surface N-cadherin. Importantly, surface N-cadherin elevation is specifically required for the maintenance of nascent dendrite arbors. Through loss-and gain-of-function approaches, we showed that N-cadherin-mediated dendrite growth requires association of the cadherin/catenin complex with the actin cytoskeleton. In summary, these results identify a previously unexplored and specific function for activity-induced, N-cadherin-mediated neuron-neuron contacts in the maintenance of dendrite arbors.cell adhesion molecule | catenin | actin D endrite growth and development are regulated by a combination of intrinsic programs and extrinsic signals, including neuronal activity, neurotrophins, morphogens, guidance cues, and cell adhesion molecules (CAMs), such as classical and seven-pass transmembrane cadherins (1-4). The establishment and maintenance of synaptic contacts between axons and dendrites also depend on CAMs, including neurexins/neurligins, EphB/ephrin-Bs, Neural-cadherin (N-cadherin), Ig superfamily members, and leucine-rich repeat containing synaptic adhesion molecules (5, 6). Importantly, the processes of axon/dendrite development and synapse formation are tightly correlated and regulated by neuronal activity (1,7). N-cadherin is a transmembrane CAM that interacts in a homophilic Ca 2+ -dependent manner through its extracellular ectodomains (8). Together with β-catenin and αN-catenin, it forms the cadherin/catenin complex, a main complex linking the extracellular environment to the actin cytoskeleton (9). The cadherin/catenin complex is present at high levels in both axons and dendrites (10), forming adherens junctions in epithelial cells and synaptic junctions in neurons.In the present study, we examined the function of N-cadherinmediated cell-cell interaction in the stabilization of dendritic arbors and in activity-dependent enhancement of dendritogenesis. Using a soluble N-cadherin ectodomain, we demonstrated a requirement for N-cadherin-mediated extracellular interaction in activity-dependent dendrite growth. Furthermore, by plating neurons in isolation, we showed that cell-cell contact is required for activity and N-cadherin-dependent dendrite growth. Finally, we showed that neuronal activity elevated surface N-cadherin level, an effect required for the maintenance of dendrite arbors. Together, these results identify a previously unexplored and specific function for activity-induced elevation of surface N-cadherin in the ma...

Actin Aggregations Mark the Sites of Neurite Initiation

“…High-density mixed neuronal-glial cultures were prepared from SpragueDawley rat pups on postnatal day 0 (P0) as previously described [49,50]. Briefly, hippocampi, with the dentate gyri removed, were dissected, and dissociated neurons were plated on glass coverslips (63- For dentate granule cell cultures, only the dentate gyrus was cultured, and Prox 1 immunostaining was used to confirm the identity of the granule cells.…”

“…The lateral ventricles of E15.5 embryos were injected with 2 lL Qiagen Maxiprep DNA and Fast Green dye using a pulled micropipette. The following plasmids were used: pCMV-LifeAct-TagRFP [51] (3 lg/lL; 60102, ibidi GmbH, Martinsried, Germany), GFP-actinin [52] (3 lg/lL), tdTomato [53] (0.5 lg/lL; 22478, Addgene, Cambridge, MA; originally named FUtdTW), and pCS2 min-GFP [49] (1 lg/lL). Forceps-type electrode paddles controlled by an ECM 830 electroporator (BTX Instrument Division, Harvard Apparatus Inc, Holliston, MA) were used to deliver 5 pulses at 60 mV with 50 ms duration at 100 ms intervals.…”

CRP1, a Protein Localized in Filopodia of Growth Cones, Is Involved in Dendritic Growth

“…Because our data showed that CRP1 is required for dendritic growth in neurons, we hypothesized that CRP1 may act as a mediator for dendritic growth induced by Ca 2ϩ influx. It has been reported that when neurons were depolarized with KCl at 3 DIV, enhanced dendritic growth is observed in both cortical neurons and hippocampal neurons (Redmond et al, 2002;Tan et al, 2010). We first measured CRP1 expression in cultured hippocampal neurons after depolarization using the same condition as reported previously (Redmond et al, 2002).…”

Rare autosomal copy number variations in early-onset familial Alzheimer’s disease

“…The 488-kb gain in CN encompasses CDH2, encoding N-cadherin, which is expressed in brain, skeletal and cardiac muscles and has critical roles in synaptic adhesion, dendritic morphology and neuritic growth. [55][56][57][58][59] CDH2 has been extensively studied in AD. For example, inhibition of N-cadherin function has been reported to accelerate Ab-triggered synapse damage.…”