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Rudnick, Gary, Kraemer, Reinhard, Blakely, Randy D., Murphy, Dennis L. and Verrey, Francois ORCID: 0000-0003-3250-9824 (2014). The SLC6 transporters: perspectives on structure, functions, regulation, and models for transporter dysfunction. Pflugers Arch., 466 (1). S. 25 - 43. NEW YORK: SPRINGER. ISSN 1432-2013

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Abstract

The human SLC6 family is composed of approximately 20 structurally related symporters (co-transporters) that use the transmembrane electrochemical gradient to actively import their substrates into cells. Approximately half of the substrates of these transporters are amino acids, with others transporting biogenic amines and/or closely related compounds, such as nutrients and compatible osmolytes. In this short review, five leaders in the field discuss a number of currently important research themes that involve SLC6 transporters, highlighting the integrative role they play across a wide spectrum of different functions. The first essay, by Gary Rudnick, describes the molecular mechanism of their coupled transport which is being progressively better understood based on new crystal structures, functional studies, and modeling. Next, the question of multiple levels of transporter regulation is discussed by Reinhard Kramer, in the context of osmoregulation and stress response by the related bacterial betaine transporter BetP. The role of selected members of the human SLC6 family that function as nutrient amino acid transporters is then reviewed by Fran double dagger ois Verrey. He discusses how some of these transporters mediate the active uptake of (essential) amino acids into epithelial cells of the gut and the kidney tubule to support systemic amino acid requirements, whereas others are expressed in specific cells to support their specialized metabolism and/or growth. The most extensively studied members of the human SLC6 family are neurotransmitter reuptake transporters, many of which are important drug targets for the treatment of neuropsychiatric disorders. Randy Blakely discusses the role of posttranscriptional modifications of these proteins in regulating transporter subcellular localization and activity state. Finally, Dennis Murphy reviews how natural gene variants and mouse genetic models display consistent behavioral alterations that relate to altered extracellular neurotransmitter levels.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rudnick, Gary UNSPECIFIED UNSPECIFIED UNSPECIFIED Kraemer, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Blakely, Randy D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Murphy, Dennis L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Verrey, Francois UNSPECIFIED orcid.org/0000-0003-3250-9824 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-451523
DOI:	10.1007/s00424-013-1410-1
Journal or Publication Title:	Pflugers Arch.
Volume:	466
Number:	1
Page Range:	S. 25 - 43
Date:	2014
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-2013
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TRAFFICKING-INDEPENDENT REGULATION; GLYCINE BETAINE UPTAKE; DOPAMINE D2 RECEPTOR; AMINO-ACID-TRANSPORT; SEROTONIN TRANSPORTER; NEUROTRANSMITTER TRANSPORTERS; CORYNEBACTERIUM-GLUTAMICUM; NOREPINEPHRINE TRANSPORTER; PROTEIN-KINASE; ALTERNATING-ACCESS Multiple languages Physiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/45152