Modulating Neuromodulation by Receptor Membrane Traffic in the Endocytic Pathway

Mark von Zastrow, John T. Williams

Research output: Contribution to journalReview article

34 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)22-32
Number of pages11
JournalNeuron
Volume76
Issue number1
DOIs
StatePublished - Oct 4 2012

ASJC Scopus subject areas

  • Neuroscience(all)

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