When transporters fail to be transported:how to rescue folding-deficient SLC6 transporters

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When transporters fail to be transported: how to rescue folding-deficient SLC6 transporters

The human dopamine transporter (hDAT) belongs to the solute carrier 6 (SLC6) gene family. Point mutations in hDAT (SLC6A3) have been linked to a syndrome of dopamine transporter deficiency or infantile dystonia/parkinsonism. The mutations impair DAT folding, causing retention of variant DATs in the endoplasmic reticulum and subsequently impair transport activity. The folding trajectory of DAT i...

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Relax, Cool Down and Scaffold: How to Restore Surface Expression of Folding-Deficient Mutant GPCRs and SLC6 Transporters

Many diseases arise from mutations, which impair protein folding. The study of folding-deficient variants of G protein-coupled receptors and solute carrier 6 (SLC6) transporters has shed light on the folding trajectory, how it is monitored and how misfolding can be remedied. Reducing the temperature lowers the energy barrier between folding intermediates and thereby eliminates stalling along th...

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SLC6 neurotransmitter transporters: structure, function, and regulation.

The neurotransmitter transporters (NTTs) belonging to the solute carrier 6 (SLC6) gene family (also referred to as the neurotransmitter-sodium-symporter family or Na(+)/Cl(-)-dependent transporters) comprise a group of nine sodium- and chloride-dependent plasma membrane transporters for the monoamine neurotransmitters serotonin (5-hydroxytryptamine), dopamine, and norepinephrine, and the amino ...

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How structural elements evolving from bacterial to human SLC6 transporters enabled new functional properties

BACKGROUND Much of the structure-based mechanistic understandings of the function of SLC6A neurotransmitter transporters emerged from the study of their bacterial LeuT-fold homologs. It has become evident, however, that structural differences such as the long N- and C-termini of the eukaryotic neurotransmitter transporters are involved in an expanded set of functional properties to the eukaryot...

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Listening to Neurotransmitter Transporters

However, the conducting properties of transporters go well beyond this simple picture (Sonders and Amara, Division of Biology California Institute of Technology 1996). For example, the 5-HT transporter is not electro-genic; yet it displays at least four distinct conducting Pasadena, California 91125 states (Mager et al., 1994). Three of these states are permeable to Na ϩ ions, and the other to ...

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ژورنال

عنوان ژورنال: Journal of Neurology and Neuromedicine

سال: 2016

ISSN: 2572-942X

DOI: 10.29245/2572.942x/2016/9.1098