SLC10A4 Membrane Protein Introduction

Introduction of SLC10A4

SLC10A4 belongs to the sodium bile acid cotransporter family whose members are the Na(+)/taurocholate co-transporting polypeptide (NTCP, SLC10A1) and the apical sodium-dependent bile acid transporter (ASBT, SLC10A2). SLC10A4 is a novel member of the SLC10 carrier family with the highest phylogenetic relationship to NTCP. This protein is encoded by SLC10A4 gene in human, with 437 amino acids with a predicted molecular mass of 46.5 kDa. SLC10A4 shares amino identity with other members of the sodium bile acid symporter family (SLC10A2, SLC10A1, SLC10A3, and SLC10A5) and is conserved amongst various mammalian species.

Function of SLC10A4 Membrane Protein

SLC10A4 belongs to the sodium-bile acid cotransporter family (Slc10) but does not show plasma membrane transport activity of bile acids and related molecules. It has been reported that SLC10A4 is found in synaptic vesicles of cholinergic and monoaminergic neurons of the peripheral and central nervous system, suggesting a transport function for any kind of neurotransmitter. Furthermore, SLC10A4 has been shown as a vesicular monoamine and cholinergic transporter, which functions a role in the homeostasis and neuromodulation of dopamine in the body. The deficiency of SLC10A4 has associated with a decreased dopamine vesicular uptake. In view of the role and discovery of SLC10A4 in dopaminergic signaling, it shows a novel mechanism for neuromodulation and represents an unexplored target for the treatment of neurological and mental disorders.

Fig.1 SLC10A4 is a vesicular aminergic associated transporter modulating monoamine homeostasis. (Larhammar, 2015)

Application of SLC10A4 Membrane Protein in Literature

1. Schmidt S., et al. Expression, sorting and transport studies for the orphan carrier SLC10A4 in neuronal and non-neuronal cell lines and in Xenopus laevis oocytes. Bmc Neuroscience. 2015, 16(1):35. PubMed ID: 26084360
   
   

   This study indicates that SLC10A4 does not seem to represent a typical neurotransmitter transporter such as DAT, SERT, CHT1 or VMAT2.

2. Splinter P.L., et al. Cloning and expression of SLC10A4, a putative organic anion transport protein. World Journal of Gastroenterology. 2006, 12(42):6797-805. PubMed ID: 17106928
   
   

   In this article, authors suggest that SLC10A4 has no ability to transport taurocholate. However, this protein may be involved in the transportation of other endogenous organic anions due to its wide tissue distribution.

3. Abe T., et al. SLC10A4 is a protease-activated transporter that transports bile acids. Journal of Biochemistry. 2013, 154(1):93-101. PubMed ID: 23589386
   
   

   These results show that SLC10A4 may have low activity but becomes activated by proteases, including thrombin, following cleavage. This also demonstrates that SLC10A4 seems to be a protease-activated transporter and transports bile acids.

4. Popova S.N. and Alafuzoff I. Distribution of SLC10A4, a synaptic vesicle protein in the human brain, and the association of this protein with Alzheimer's disease-related neuronal degeneration. Journal of Alzheimers Disease. 2013, 37(3):603-610. PubMed ID: 23948907
   
   

   This research shows that depletion of SLC10A4 is present in the brain with increased severity of Alzheimer's disease-related neuronal degeneration.

5. Larhammar M., et al. SLC10A4 is a vesicular amine-associated transporter modulating dopamine homeostasis. Biol Psychiatry. 2015, 77(6):526-36. PubMed ID: 25176177
   
   

   These results demonstrate that SLC10A4 is a vesicular monoaminergic and cholinergic associated transporter that is important for dopamine homeostasis and neuromodulation in vivo. The discovery of SLC10A4 and its role in dopaminergic signaling reveals a novel mechanism for neuromodulation and represents an unexplored target for the treatment of neurological and mental disorders.

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Reference

1. Larhammar M, et al. (2015). SLC10A4 is a vesicular amine-associated transporter modulating dopamine homeostasis. Biol Psychiatry. 77(6), 526-36.

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