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9.B.16 The Putative Ductin Channel (Ductin) Family

Ductin is believed to be a highly conserved multifunctional protein serving as 1) the subunit c or proteolipid component of eukaryotic vacuolar and archaeal H -translocating ATPases (TC #3.A.2), 2) the channel-forming protein component of a form of gap junction in metazoan animals (TC #1.A.24), and 3) a putative neurotransmitter release channel, the ''''Mediatophore complex,'''' in synaptic vesicles of animals. Ductin consists of a four transmembrane helix bundle and arose by intragenic duplication of a 2 TMS-encoding genetic unit equivalent to the gene encoding the c-subunits of F-type ATPases (TC #3.A.2). Ductin complexes can transport molecules as large as acetyl choline and glutamate. The ductin pore in V-type ATPases may not provide the pathway for the transport of protons and has been suggested to instead accomodate the polypeptide chains of the stalk. Yeast (S. cerevisiae) contains three ductin paralogues, VMA11, TFP3 and PPA1.

Ca2 -dependent acetylcholine release in: i) proteoliposomes, ii) Xenopus oocytes, and iii) release-deficient cell lines is dependent on the expression of the mediatophore, a protein isolated from the plasma membrane of cholinergic nerve terminals of the Torpedo electric organ. The role of the mediatophore in quantal acetylcholine release, its possible involvement in morphological changes affecting presynaptic membrane during the release, and its interactions with others proteins of the cholinergic nerve terminal has been discussed (Bloc et al. 2000).

Immunological stimulation of T cells by phytohemagglutinin (PHA) enhances the synthesis and release of acetylcholine (ACh). Mediatophore, a homooligomer of a 16-kDa subunit homologous to the proteolipid subunit c of vacuolar H -ATPase mediates ACh release from T cells (Tomina and Takahata 2012). Mediatophore protein is present in the cytoplasm and on the plasma membrane of T cells. Mediatophore gene expression is up-regulated by immunological T cell activation by PHA, and anti-mediatophore small interference RNA down-regulated mediatophore gene expression, significantly reducing ACh release. Thus, T cells express mediatophore, which then plays a key role in mediating ACh release, and mediatophore expression is regulated by immunological stimulation.  Mediatophore, identical to the c-subunit in V-type ATPases, ATP6V0C, also mediates dopamine release from nerve terminals in the striatum of DA neurons (Jin et al. 2012).

The generalized transport reaction proposed for ductin or mediatophore is:

Small molecules (cytoplasm) small molecules (out or cytoplasm of an adjacent cell)

References associated with 9.B.16 family:

Birman, S., F.M. Meunier, B. Lesbats, J.P. Le Caer, J. Rossier, and M. Israël. (1990). A 15 kDa proteolipid found in mediatophore preparations from Torpedo electric organ presents high sequence homology with the bovine chromaffin granule protonophore. FEBS Lett. 261: 303-306. 2155824
Bloc, A., V. Bancila, M. Israël, and Y. Dunant. (2000). Reconstitution of mediatophore-supported quantal acetylcholine release. Metab Brain Dis 15: 1-16. 10885537
Finbow, M.D., M. Harrison and P. Jones (1995). Ductin - a proton pump component, a gap junction channel and a neurotransmitter release channel. BioEssays 17:247-255. 7538293
Jin, D., S. Muramatsu, N. Shimizu, S. Yokoyama, H. Hirai, K. Yamada, H.X. Liu, C. Higashida, M. Hashii, A. Higashida, M. Asano, S. Ohkuma, and H. Higashida. (2012). Dopamine release via the vacuolar ATPase V0 sector c-subunit, confirmed in N18 neuroblastoma cells, results in behavioral recovery in hemiparkinsonian mice. Neurochem Int 61: 907-912. 22265874
Tomina, Y. and M. Takahata. (2012). Discrimination learning with light stimuli in restrained American lobster. Behav Brain Res 229: 91-105. 22245256