Department of Psychiatry, University of California at San Francisco, San Francisco, CA 94158, USA.
Neuron. 2012 Oct 4;76(1):22-32. doi: 10.1016/j.neuron.2012.09.022.
Cellular responsiveness to many neuromodulators is controlled by endocytosis of the transmembrane receptors that transduce their effects. Endocytic membrane trafficking of particular neuromodulator receptors exhibits remarkable diversity and specificity, determined largely by molecular sorting operations that guide receptors at trafficking branchpoints after endocytosis. In this Review, we discuss recent progress in elucidating mechanisms mediating the molecular sorting of neuromodulator receptors in the endocytic pathway. There is emerging evidence that endocytic trafficking of neuromodulator receptors, in addition to influencing longer-term cellular responsiveness under conditions of prolonged or repeated activation, may also affect the acute response. Physiological and pathological consequences of defined receptor trafficking events are only now being elucidated, but it is already apparent that endocytosis of neuromodulator receptors has a significant impact on the actions of therapeutic drugs. The present data also suggest, conversely, that mechanisms of receptor endocytosis and molecular sorting may themselves represent promising targets for therapeutic manipulation.
细胞对许多神经调质的反应性受转导其作用的跨膜受体的内吞作用控制。特定神经调质受体的内吞膜运输表现出显著的多样性和特异性，这主要取决于分子分拣操作，这些操作在受体内吞后在运输分支点引导受体。在这篇综述中，我们讨论了阐明介导神经调质受体在胞吞途径中分子分拣的机制的最新进展。有越来越多的证据表明，除了在长期或重复激活的情况下影响长期的细胞反应性外，神经调质受体的胞吞作用也可能影响急性反应。目前正在阐明特定受体运输事件的生理和病理后果，但很明显，神经调质受体的内吞作用对治疗药物的作用有重大影响。目前的数据还表明，相反，受体内吞和分子分拣的机制本身可能代表治疗干预的有希望的靶点。
