A new look at calcium channel α2δ subunits.
The classical roles of α(2)δ proteins are as accessory calcium channel subunits, enhancing channel trafficking. They were thought to have type-I transmembrane topology, but we find that they can form GPI-anchored proteins. Moreover α(2)δ-1 and α(2)δ-3 have been shown to have novel functions in synaptogenesis, independent of their effect on calcium channels. In neurons, the α(2)δ-1 subunits are present mainly in presynaptic terminals. Peripheral sensory nerve injury results in the up-regulation of α(2)δ-1 in dorsal root ganglion (DRG) neurons, and there is a consequent increase in trafficking of α(2)δ-1 to their terminals. Furthermore, gabapentinoid drugs, which bind to α(2)δ-1 and α(2)δ-2, not only impair their trafficking, but also affect α(2)δ-1-dependent synaptogenesis. These drugs may interfere with α(2)δ function at several different levels.
Bauer
Claudia S
CS
Department of Neuroscience, Physiology and Pharmacology, University College London, London, WC1E 6BT, UK.
Tran-Van-Minh
Alexandra
A
Kadurin
Ivan
I
Dolphin
Annette C
AC
D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology*; D005727:Ganglia, Spinal / Q000737:chemistry / Q000166:cytology / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D017729:Presynaptic Terminals / Q000737:chemistry / Q000473:pathology / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D011984:Sensory Receptor Cells / Q000737:chemistry / Q000473:pathology / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
C425903:CACNA2D1 protein, human; D015220:Calcium Channels; C494035:voltage gated calcium channel subunit Ca alpha2delta-1, human