Cholesterol transporter protein that regulates cell membranes probably played an important role in vertebrate evolution

The ABCA1 protein transfers cholesterol from the inner to the outer layer of the cell membrane. This strengthens the skin’s ability to protect the body from external stimuli. Researchers suggest that this played an important role in the evolution of vertebrates. Credits: iCeMS MindyTakamiya / Kyoto University

Nearly four decades of research have led scientists from Japan’s Institute for Integrated Cellular Materials Science (iCeMS) to suggest that the carrier protein family has played an important role in species evolution. One protein in particular, called ABCA1, was probably crucial for vertebrate evolution by aiding in regulation when signals involved in cell proliferation, differentiation, and migration enter the cell. This process was necessary for vertebrates to develop into more complex organisms with a sophisticated body structure.

ATP-binding cassette proteins (ABCs) are very similar among species, including bacteria, plants, and animals. There are different types of ABC proteins with different transport roles, which import nutrients into cells, export toxic compounds outside them and regulate the concentration of lipids in cell membranes.

iCeMS cell biochemist Kazumitsu Ueda has been studying human ABC proteins for 35 years, since he and his colleagues identified the first gene for the eukaryotic ABC protein.

“We believe that ABC proteins must have played an important role in evolution,” says Ueda. “By transporting lipids, they have allowed plants and animals to thrive on land by protecting them from water loss and infection with pathogens. They are also thought to have accelerated vertebrate evolution by allowing cholesterol to function as a signaling molecule within the membrane.”

Organisms that existed early in the Earth’s history probably originated from DNA and proteins surrounded by an impermeable lipid membrane. As organisms evolved, their membranes were reinforced to protect them from the external environment. But that meant that only organisms that developed special ABC transporters capable of carrying nutrients across the membrane survived. ABC proteins also played an important role in creating an outer membrane that protected cells from external stresses and in removing harmful substances from within.

Recently, Ueda and his team studied the roles of ABCA1, gaining a deeper insight into how it regulates cholesterol. In particular, they found that ABCA1 exports cellular phospholipids and cholesterol outside the cell to make high-density lipoproteins, popularly called good cholesterol.

They also found that ABCA1 continuously transfers cholesterol from the inner leaflet of the cell membrane to the outer leaflet, maintaining a lower concentration on the inner side. This buoyancy is temporarily suppressed when the cell is exposed to an external stimulus, such as growth hormone. The resulting accumulation of cholesterol in the inner leaflet triggers the recruitment of proteins into the membrane and modulates signal transduction. Ueda and his team suggest that ABCA1 allowed vertebrates to develop complicated biological processes and sophisticated bodies.

“ABCA1 is very unique and its functions surprised us,” says Ueda. “The role of cholesterol was thought to focus mainly on physically strengthening the cell membrane and reducing its permeability to ions. Our research suggests that it played a more important role in vertebrates, accelerating their evolution.”

Molecular view of HDL formation

More information:
Fumihiko Ogasawara et al. ABC proteins in evolution, FEBS words (2020). DOI: 10.1002 / 1873-3468.13945

Provided by the University of Kyoto

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