Investigating polymorphisms in membrane-associated transporter protein SLC45A2, using sucrose transporters as a model

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Abstract

Solute carrier family 45 member 2 encodes the melanosomal membrane protein, membrane-associated transporter protein (MATP), of unknown function, that is required for normal melanin synthesis. The present study analyzed the effects of two human MATP mutations, D93N, which causes oculocutaneous albinism 4 (OCA4), and L374F, which is correlated with light pigmentation in European populations. Corresponding mutations were produced in the related and well-characterized sucrose transporter from rice, OsSUT1, and transport activity was measured by heterologous expression in Xenopus laevis oocytes, in addition to 14C-sucrose uptake in yeast. The mutation corresponding to D93N resulted in a complete loss of transport activity. The mutation corresponding to L374F resulted in a 90% decrease in transport activity, although the substrate affinity was unaffected. The results indicated that the D93N mutation causes OCA4 as a result of loss of MATP transport activity, and that the F374 allele confers significantly lower transport activity than L374.

Original languageEnglish (US)
Pages (from-to)1393-1398
Number of pages6
JournalMolecular medicine reports
Volume12
Issue number1
DOIs
StatePublished - Jul 1 2015

Fingerprint

Membrane Transport Proteins
Polymorphism
Sucrose
Membrane Proteins
Membranes
Mutation
Oculocutaneous Albinism
Melanins
Yeast
Proteins
Substrates
Xenopus laevis
Pigmentation
Protein Transport
Oocytes
Yeasts
Alleles
Light
Population
human SLC45A2 protein

Keywords

  • Melanosome
  • Membrane-associated transporter protein
  • Oculocutaneous albinism 4
  • Solute carrier family 45 member 2
  • Sucrose transporter

Cite this

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title = "Investigating polymorphisms in membrane-associated transporter protein SLC45A2, using sucrose transporters as a model",
abstract = "Solute carrier family 45 member 2 encodes the melanosomal membrane protein, membrane-associated transporter protein (MATP), of unknown function, that is required for normal melanin synthesis. The present study analyzed the effects of two human MATP mutations, D93N, which causes oculocutaneous albinism 4 (OCA4), and L374F, which is correlated with light pigmentation in European populations. Corresponding mutations were produced in the related and well-characterized sucrose transporter from rice, OsSUT1, and transport activity was measured by heterologous expression in Xenopus laevis oocytes, in addition to 14C-sucrose uptake in yeast. The mutation corresponding to D93N resulted in a complete loss of transport activity. The mutation corresponding to L374F resulted in a 90{\%} decrease in transport activity, although the substrate affinity was unaffected. The results indicated that the D93N mutation causes OCA4 as a result of loss of MATP transport activity, and that the F374 allele confers significantly lower transport activity than L374.",
keywords = "Melanosome, Membrane-associated transporter protein, Oculocutaneous albinism 4, Solute carrier family 45 member 2, Sucrose transporter",
author = "Anke Reinders and Ward, {John M.}",
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AU - Reinders, Anke

AU - Ward, John M.

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N2 - Solute carrier family 45 member 2 encodes the melanosomal membrane protein, membrane-associated transporter protein (MATP), of unknown function, that is required for normal melanin synthesis. The present study analyzed the effects of two human MATP mutations, D93N, which causes oculocutaneous albinism 4 (OCA4), and L374F, which is correlated with light pigmentation in European populations. Corresponding mutations were produced in the related and well-characterized sucrose transporter from rice, OsSUT1, and transport activity was measured by heterologous expression in Xenopus laevis oocytes, in addition to 14C-sucrose uptake in yeast. The mutation corresponding to D93N resulted in a complete loss of transport activity. The mutation corresponding to L374F resulted in a 90% decrease in transport activity, although the substrate affinity was unaffected. The results indicated that the D93N mutation causes OCA4 as a result of loss of MATP transport activity, and that the F374 allele confers significantly lower transport activity than L374.

AB - Solute carrier family 45 member 2 encodes the melanosomal membrane protein, membrane-associated transporter protein (MATP), of unknown function, that is required for normal melanin synthesis. The present study analyzed the effects of two human MATP mutations, D93N, which causes oculocutaneous albinism 4 (OCA4), and L374F, which is correlated with light pigmentation in European populations. Corresponding mutations were produced in the related and well-characterized sucrose transporter from rice, OsSUT1, and transport activity was measured by heterologous expression in Xenopus laevis oocytes, in addition to 14C-sucrose uptake in yeast. The mutation corresponding to D93N resulted in a complete loss of transport activity. The mutation corresponding to L374F resulted in a 90% decrease in transport activity, although the substrate affinity was unaffected. The results indicated that the D93N mutation causes OCA4 as a result of loss of MATP transport activity, and that the F374 allele confers significantly lower transport activity than L374.

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KW - Membrane-associated transporter protein

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KW - Solute carrier family 45 member 2

KW - Sucrose transporter

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