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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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Regulation of Nuclear Protein Sorting01:45

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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
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The Significance of Membrane Transport01:44

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The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
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Hepatic Drug Clearance: Role of Transporters01:14

Hepatic Drug Clearance: Role of Transporters

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In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
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Receptor-mediated Endocytosis01:39

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Related Experiment Video

Updated: Jun 4, 2025

Ion Mobility-Mass Spectrometry Techniques for Determining the Structure and Mechanisms of Metal Ion Recognition and Redox Activity of Metal Binding Oligopeptides
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Ion Mobility-Mass Spectrometry Techniques for Determining the Structure and Mechanisms of Metal Ion Recognition and Redox Activity of Metal Binding Oligopeptides

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Human transporter de-oligomerization regulates copper uptake into cells.

Tai-Yen Chen1, Meng-Hsuan Wen1, Huanhuan Chen1

  • 1University of Houston.

Research Square
|December 23, 2024
PubMed
Summary

Excess copper causes the CTR1 transporter to break apart into single units, rapidly stopping copper uptake and preventing cell damage. This structural change is key to maintaining copper balance.

Keywords:
CTR1OligomerizationRab5copper transportendocytosissingle-molecule localization microscopysingle-molecule neighbor density analysis

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Ion Mobility-Mass Spectrometry Techniques for Determining the Structure and Mechanisms of Metal Ion Recognition and Redox Activity of Metal Binding Oligopeptides
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Author Spotlight: Exploring Cellular Zinc Regulation Through ZnT1 Functionality
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Author Spotlight: Exploring Cellular Zinc Regulation Through ZnT1 Functionality

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Copper is vital for cellular functions like energy production and antioxidant defense.
  • Dysregulated copper levels can cause toxicity and disease.
  • Copper Transporter 1 (CTR1) is crucial for cellular copper uptake and homeostasis.

Purpose of the Study:

  • To investigate the mechanism of rapid regulation of cellular copper uptake by CTR1.
  • To understand how CTR1 responds to excess copper levels.

Main Methods:

  • Single-molecule localization microscopy (SMLM) was employed to visualize CTR1 dynamics.
  • Single-molecule neighbor density assays were used to quantify CTR1 clustering and monomerization.
  • An endocytosis-deficient CTR1 mutant (M150L) was utilized for comparison.

Main Results:

  • Excess copper induces the dissociation of trimeric CTR1 into monomers.
  • This monomerization event precedes CTR1 endocytosis.
  • The endocytosis-deficient CTR1 (M150L) mutant showed a blockage in copper-induced monomerization.
  • CTR1 monomerization was identified as a rapid mechanism to halt copper uptake.

Conclusions:

  • Protein oligomerization state changes represent a novel regulatory mechanism for metal transporters.
  • CTR1 structural changes (trimer to monomer) are directly linked to its endocytosis and cellular copper homeostasis.
  • This study provides new insights into preventing copper overload at the cellular level.