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Related Concept Videos

Carrier-Mediated Transport01:06

Carrier-Mediated Transport

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Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
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Active Transport01:14

Active Transport

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Active transport is a critical biological process that allows cells to move solutes against an electrochemical gradient. This process requires direct energy input and is characterized by its selectivity, saturability, and susceptibility to competitive inhibition.
Primary active transporters, like Na+, K+ and -ATPase, directly utilize ATP to move ions across the membrane. These transporters play significant roles in various physiological processes. For instance, Na+, K+ and -ATPase maintain...
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Secondary Active Transport01:55

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One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme “pump” embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
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The ADP/ATP Carrier Protein01:42

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ADP/ATP carrier or AAC protein is the most abundant carrier protein in the inner mitochondrial membrane. It transports large quantities of ADP and ATP, equivalent to the average human body weight, every day. Among other transporters, ACC protein is one of the best-studied members of the mitochondrial carrier protein family. The ADP/ATP carrier protein comprises two transmembrane helices connected to a loop and a single alpha-helix on the matrix side. It switches between two conformational...
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Facilitated Diffusion01:16

Facilitated Diffusion

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The plasma membrane, a critical structure in cellular biology, houses an array of transporters, or carrier proteins, interspersed within its lipid bilayer. These proteins play a crucial role in solute transport through facilitated diffusion, a form of passive diffusion that uses transporters to move the molecules across the membrane.
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...
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Primary Active Transport01:29

Primary Active Transport

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In contrast to passive transport, active transport involves a substance being moved through membranes in a direction against its concentration or electrochemical gradient. There are two types of active transport: primary active transport and secondary active transport. Primary active transport utilizes chemical energy from ATP to drive protein pumps embedded in the cell membrane. With energy from ATP, the pumps transport ions against their electrochemical gradients—a direction they would...
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Related Experiment Video

Updated: Jun 3, 2025

A Proteoliposome-Based Efflux Assay to Determine Single-molecule Properties of Cl- Channels and Transporters
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A creatine efflux transporter in oligodendrocytes.

Svenja Flögel1, Miriam Strater1, Dietmar Fischer1

  • 1Department of Pharmacology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Germany.

The FEBS Journal
|January 10, 2025
PubMed
Summary

Researchers identified SLC22A15 as a key transporter for controlled creatine release from brain cells. This discovery addresses a crucial gap in understanding creatine metabolism and its role in preventing neurodevelopmental impairments.

Keywords:
SLC22A15creatine transportermacrophagemass spectrometryoligodendrocyte

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Creatine is vital for ATP regeneration in high-energy-demand cells, and its deficiency causes neurodevelopmental issues.
  • Oligodendrocytes synthesize creatine in the brain to supply neurons, with uptake mediated by SLC6A8, but release mechanisms remained unknown.
  • Understanding creatine release is critical for brain energy metabolism and preventing neurological disorders.

Purpose of the Study:

  • To investigate the function of the highly conserved transporter SLC22A15 in creatine release.
  • To determine if SLC22A15 mediates the controlled release of creatine from producing cells, particularly oligodendrocytes.
  • To elucidate the regulatory mechanisms and cellular localization of SLC22A15 in creatine transport.

Main Methods:

  • Heterologous expression of human and rat SLC22A15 in 293 cells.
  • Analysis of substrate release using mass spectrometry.
  • Examination of SLC22A15 mRNA expression profiles in human and mouse tissues and single-cell RNA sequencing data.

Main Results:

  • SLC22A15 was identified as a transporter of various zwitterions, with creatine efflux significantly exceeding other substrates.
  • SLC22A15 is regulated and inactive by default, preventing uncontrolled creatine loss, and can be triggered by external substrates for one-to-one exchange.
  • SLC22A15 expression is highest in oligodendrocytes and macrophages, correlating with high intracellular creatine synthesis enzyme (AGAT and GAMT) levels, unlike in proximal tubular cells and hepatocytes.

Conclusions:

  • SLC22A15 is established as the pivotal transporter for regulated creatine release from oligodendrocytes.
  • This finding fills a critical knowledge gap in brain creatine metabolism and transport.
  • The regulated release mechanism mediated by SLC22A15 is crucial for maintaining neuronal energy homeostasis and preventing neurodevelopmental impairments.