Lipid News

Progress in identifying lipid domains (rafts) in living cells

Erwin London
By Erwin London
August 01, 2017

Under which conditions lipid chemical heterogeneity results in the formation of coexisting lipid domains with distinct lipid compositions and properties in living cells has been a subject of intense research for decades.

In model membrane formed from lipid mixtures, spontaneous formation of tightly packed sphingolipid- and cholesterol-rich lipid domains (in the liquid-ordered state) that segregate from loosely packed domains richer in unsaturated phospholipids (in the liquid-disordered state) are detected and characterized easily.
lipidraft.png

However, analogous domains in cells are very small under most conditions — at or beyond the limit of detection for most techniques. This has led to much controversy as well as much work aiming to develop new methods to identify and characterize tiny nanodomains.

Very recent progress in living cells has been encouraging on several fronts. Studies using novel fluorescently labeled lipids with affinities for liquid-ordered domains similar to those of unlabeled lipids have revealed that specific association of raft-loving lipids with raft-localizing proteins occurs in living cells (1,2). Single-particle-tracking measurements show that these interactions are lost in living cells when even minor changes in lipid or protein structure are made if these changes abolish raft-associating physical properties.

In other studies, super-resolution microscopy in B cells has found co-localization of raft markers with, and exclusion of nonraft markers from, the vicinity of clustered B-cell receptors on a size scale similar to that of the clusters (50 nanometers to 100 nanometers). This is indicative of the formation of ordered domains around the B-cell receptors. An analogous formation of nanodomains was detected around clustered cholera toxin, a molecule long known to induce the formation of ordered domains in vitro and in cells (3).

These studies extend previous work from other labs that reported lipid-domain-based molecular interactions in these systems. This is indicative of a robust underlying phenomenon.

Advances leading to an increased ability to visualize domains and manipulate their structure promise further progress. An even higher-resolution, super-resolution microscopy approach has been developed, which may allow visualization of domains that otherwise would elude direct visualization (4).

Finally, our own lab has devised a method efficiently to replace virtually the entire complement of plasma membrane outer leaflet lipids in living cells with exogenous lipids. This may allow fine-tuned control of domain formation and properties (5).

REFERENCES

1. Komura, N. et al. Nat. Chem. Biol. 12, 402 – 410 (2016).
2. Kinoshita, M. et al. J. Cell. Biol. 216, 1183 – 1204 (2017).
3. Stone, M.B. et al. eLife 6, e19891 (2017).
4. Balzarotti, F. et al. Science 355, 606 – 612 (2017).
5. Li, G. et al. Proc. Natl. Acad. Sci. USA 113, 14025 – 14030 (2016).

 

Erwin London
Erwin London

Erwin London is a distinguished professor in the department of biochemistry and cell biology and in the department of chemistry at Stony Brook University.

Join the ASBMB Today mailing list

Sign up to get updates on articles, interviews and events.

Latest in Science

Science highlights or most popular articles

From the journals: JBC
Journal News

From the journals: JBC

May 28, 2020

Enzymes playing hot potato with heme. A CRISPR system that cuts indiscriminately. Cholesterol levels changing ATP signaling. Read about recent papers on these topics and more in the Journal of Biological Chemistry.

How to catch and kill a coronavirus on a doorknob
News

How to catch and kill a coronavirus on a doorknob

May 27, 2020

Researchers at Miami University are developing polymer coatings to inactivate SARS-CoV-2 on public surfaces.

Corbett goes the extra mile to support young scientists
Award

Corbett goes the extra mile to support young scientists

May 26, 2020

The ASBMB honors an Emory University professor and trailblazer who is passionate about increasing diversity and inclusion in science.

Rapid home-based coronavirus tests are coming together in research labs
News

Rapid home-based coronavirus tests are coming together in research labs

May 25, 2020

The author and colleagues are working on analyzing spit using advanced CRISPR gene editing techniques.

Building a mouse squad against Covid-19
News

Building a mouse squad against Covid-19

May 24, 2020

It began with an email from Wuhan, a Maine laboratory and mouse sperm from Iowa. Now that lab is on the verge of supplying a much-needed animal for SARS-CoV-2 research.

Researchers unmask a pancreatic cancer culprit
News

Researchers unmask a pancreatic cancer culprit

May 23, 2020

Researchers have found that autophagic degradation of MHCI spurs the immune evasion of pancreatic cancer cells.