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The Significance of Membrane Transport

The Significance of Membrane Transport

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.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...

Secondary Active Transport

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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...

Secondary Active Transport

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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...

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...

Pore Transport and Ion-Pair Transport

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Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...

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: Jan 10, 2026

Functional Characterization of Na+/H+ Exchangers of Intracellular Compartments Using Proton-killing Selection to Express Them at the Plasma Membrane

Functional Characterization of Na+/H+ Exchangers of Intracellular Compartments Using Proton-killing Selection to Express Them at the Plasma Membrane

Published on: March 30, 2015

Engineering substrate selectivity in the human sodium/iodide symporter (NIS).

Alejandro Llorente-Esteban, Haswitha Sabbineni, Kendra Hoffsmith

Biorxiv : the Preprint Server for Biology

|November 24, 2025

Summary

This summary is machine-generated.

Engineered Na⁺/I⁻ symporter (NIS) mutants selectively transport oxyanions, not iodide. This allows targeted cancer therapy with radioisotopes while protecting the thyroid, expanding NIS applications beyond thyroid cancer treatment.

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Last Updated: Jan 10, 2026

Functional Characterization of Na+/H+ Exchangers of Intracellular Compartments Using Proton-killing Selection to Express Them at the Plasma Membrane

Functional Characterization of Na+/H+ Exchangers of Intracellular Compartments Using Proton-killing Selection to Express Them at the Plasma Membrane

Published on: March 30, 2015

Application of Electrophysiology Measurement to Study the Activity of Electro-Neutral Transporters

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Published on: February 3, 2018

Selection of Transporter-Targeted Inhibitory Nanobodies by Solid-Supported-Membrane SSM-Based Electrophysiology

Selection of Transporter-Targeted Inhibitory Nanobodies by Solid-Supported-Membrane SSM-Based Electrophysiology

Published on: May 3, 2021

Area of Science:

Biochemistry
Molecular Biology
Structural Biology

Background:

The Na⁺/I⁻ symporter (NIS) is crucial for thyroid hormone synthesis and radioiodide therapy for thyroid cancer.
Exogenous NIS expression in non-thyroidal cancers offers targeted therapy potential but risks thyroid damage.
A strategy is needed to selectively target cancers expressing NIS while sparing the thyroid.

Purpose of the Study:

To engineer a novel NIS variant with altered substrate specificity for targeted cancer therapy.
To investigate the structural basis of substrate selectivity in NIS.
To develop a method for selective cancer cell killing using engineered NIS and radioisotopes.

Main Methods:

Protein engineering to create a double mutant NIS (L253P/V254F, or PF-NIS).
Cryo-electron microscopy (cryo-EM) to determine the structure of PF-NIS bound to perrhenate and sodium ions.
Cell-based assays to assess iodide and oxyanion transport and cell viability.

Main Results:

The engineered PF-NIS selectively transports oxyanions (e.g., perrhenate) but not iodide.
Cryo-EM revealed the structure of PF-NIS with bound perrhenate and sodium ions at 2.58 Å resolution.
PF-NIS-expressing cells were killed by radioactive perrhenate, while non-radioactive iodide protected wild-type NIS-expressing cells.

Conclusions:

Engineered PF-NIS enables selective targeting of non-thyroidal cancers using radioisotopes like 186/188ReO4⁻.
This approach allows for targeted cancer destruction while protecting the thyroid gland.
The study provides a framework for developing NIS-based therapies with tailored substrate specificities for broader clinical applications.