Huntley George W, Gil Orlando, Bozdagi Ozlem
Fishberg Research Center for Neurobiology and the Program in Cell Adhesion, The Mount Sinai School of Medicine of New York University, NY 10029, USA.
Neuroscientist. 2002 Jun;8(3):221-33. doi: 10.1177/1073858402008003008.
Cadherins are cell adhesion molecules that are critically important for establishing brain structure and connectivity during early development. They are enriched at synapses and, by virtue of a number of properties including homophilic recognition and molecular diversity, have been implicated in the generation of synaptic specificity. Cadherins also participate in remodeling synaptic architecture and modifying the strength of the synaptic signal, thereby retaining an active role in synaptic structure, function, and plasticity, which extends beyond initial development. Cadherins have been implicated in the induction of long-term potentiation (LTP) of hippocampal synaptic strength, a cellular model for learning and memory. LTP is associated with the synthesis and recruitment of N-cadherin to newly forming synaptic junctions, induces molecular changes to N-cadherin indicative of augmented adhesive force, and can be prevented when cadherin adhesion is blocked. NMDA receptor activation, which is critically required for synaptic plasticity, may provide a signal that regulates the molecular configuration of synaptic N-cadherin, and therefore the strength of adhesion across the synaptic cleft. Additionally, there exists at the synapse a pool of surface cadherins that is untethered to the actin cytoskeleton and capable of a rapid and reversible dispersion along the plasmalemma under conditions of strong activity. These observations suggest that synaptic activity dynamically regulates both the strength and the localization of cadherin-cadherin bonds across the synaptic junctional interface, changes that may be crucial for regulating synaptic plasticity.
钙黏着蛋白是细胞黏附分子，在早期发育过程中对建立脑结构和连接至关重要。它们在突触处富集，凭借包括嗜同性识别和分子多样性在内的多种特性，参与了突触特异性的产生。钙黏着蛋白还参与重塑突触结构和调节突触信号强度，从而在突触结构、功能和可塑性方面持续发挥积极作用，这种作用超出了初始发育阶段。钙黏着蛋白与海马突触强度的长时程增强（LTP）的诱导有关，LTP是学习和记忆的细胞模型。LTP与N - 钙黏着蛋白向新形成的突触连接的合成和募集相关，诱导N - 钙黏着蛋白发生分子变化，表明黏附力增强，并且当钙黏着蛋白黏附被阻断时LTP可被阻止。NMDA受体激活是突触可塑性的关键要求，它可能提供一个信号来调节突触N - 钙黏着蛋白的分子构型，从而调节突触间隙的黏附强度。此外，在突触处存在一群表面钙黏着蛋白，它们未与肌动蛋白细胞骨架相连，并且在强活动条件下能够沿着质膜快速且可逆地分散。这些观察结果表明，突触活动动态调节突触连接界面上钙黏着蛋白 - 钙黏着蛋白键的强度和定位，这些变化可能对调节突触可塑性至关重要。
