Abstract
Voltage gated calcium channels (VGCCs) regulate neuronal excitability and translate activity into calcium dependent signaling. The α1 subunit of high voltage activated (HVA) VGCCs associates with α2δ accessory subunits, which may affect calcium channel biophysical properties, cell surface expression, localization and transport and are thus important players in calcium-dependent signaling. In vertebrates, the functions of the different combinations of the four α2δ and the seven HVA α1 subunits are incompletely understood, in particular with respect to partially redundant or separate functions in neurons. This study capitalizes on the relatively simpler situation in the Drosophila genetic model containing two neuronal putative α2δ subunits, straightjacket and CG4587, and one Cav1 and Cav2 homolog each, both with well-described functions in different compartments of identified motoneurons. Straightjacket is required for normal Cav1 and Cav2 current amplitudes and correct Cav2 channel function in all neuronal compartments. By contrast, CG4587 does not affect Cav1 or Cav2 current amplitudes or presynaptic function, but is required for correct Cav2 channel allocation to the axonal versus the dendritic domain. We suggest that the two different putative α2δ subunits are required in the same neurons to regulate different functions of VGCCs.
Highlights
Voltage gated calcium channels (VGCCs) regulate neuronal excitability and translate activity into calcium dependent signaling
Some brain parts co-express multiple α2δ subunits[28], differential spatial expression of α2δ subunits has been observed in the vertebrate brain[29,30,31,32]. It remains incompletely understood which different combinations of α2δ and α1 subunits mediate which neuronal functions, and which combinatorial codes of different α2δ/α1/β combinations regulate which subcellular aspects of high voltage activated (HVA) channel function in vivo
We find that both putative α2δ subunits mediate different functions. stj is required for normal somatodendritic Cav[1] and Cav[2] current amplitudes, as well as for correct axonal and presynaptic Cav[2] channel function
Summary
CG4587 and CG12295 are two predicted α2δ subunits in the Drosophila genome. CG12295 has been named straightjacket (stj)[37] and referred to as dα2δ336,38,39. Panneural RNAi of either putative α2δ subunit did not result in compensatory up-regulation of the other one in vivo as revealed by Western Blotting for stj following pan-neural knock down of stol and vice versa (Fig. 1D,E, genotypes: elavC155 > stolGFP/stjRNAi;UAS-dcr[2] and elavC155 > stjmCherry/stolRNAi;UAS-dcr[2]). This does not preclude compensatory capacity of one putative α2δ subunit for the other if expressed at the right place, time and strength. These data are in agreement with a reduced expression of functional Ca2+ channels in MNs axons adult DLM MNs larval crawling MNs
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