News Release

Electron microscopy reveals how vitamin A enters the cell

With a similar technology found in today's smartphone cameras -- biologists are getting new images of our cells and rapidly uncovering never-seen-before details

Peer-Reviewed Publication

Columbia University Irving Medical Center

VIDEO: Electron Microscopy Reveals How Vitamin A Enters the Cell

video: Youtube link: https://youtu.be/-277P5E9JTo

Using a new, lightning-fast camera paired with an electron microscope, Columbia University Medical Center scientists have captured images of one of the smallest proteins in our cells to be "seen" with a microscope. Using the new images, the scientists created a high-resolution model of the molecule-called STRA6 -- revealing how works to move vitamin A into our cells. view more 

Credit: Columbia University Medical Center

NEW YORK, NY (August 25, 2016)—Using a new, lightning-fast camera paired with an electron microscope, Columbia University Medical Center (CUMC) scientists have captured images of one of the smallest proteins in our cells to be “seen” with a microscope.

The protein—called STRA6—sits in the membrane of our cells and is responsible for transporting vitamin A into the cell interior. Vitamin A is essential to all mammals and is particularly important for making light receptors in our eyes, and to ensuring normal fetal development.

Images of the protein, which revealed several unusual features, were published in the August 26th issue of the journal Science, by structural biologist Filippo Mancia, PhD, assistant professor of physiology and cellular biophysics at CUMC. Dr. Mancia led a team of scientists, including Wayne Hendrickson, Larry Shapiro, Joachim Frank and Bill Blaner at CUMC, Loredana Quadro at Rutgers University, Chiara Manzini at George Washington University, and David Weber at the University of Maryland School of Medicine.

Until the new study, the way STRA6 transports vitamin A into the cell had been a mystery. Most transporters interact directly with the substances they move. But STRA6 only interacts with Vitamin A via an intermediary protein that carries the greasy vitamin A in the bloodstream. Revealing the structure of STRA6 may not only give the researchers insight into Vitamin A transport, but may also provide clues about how other related transporters work.

A new type of camera technology was key to obtaining the images of STRA6. When paired with an electron microscope, the camera allows biologists to see tiny, previously unseen structural details of the inner machinery of our cells.

“We can now get near-atomic resolution because the new camera is much faster and allows us to take a movie of the molecules,” says Oliver Clarke, PhD, an associate research scientist in the Hendrickson lab at CUMC. “Even under the electron microscope, the molecules are moving around by a tiny amount, but when you take a picture of something that is moving, the image is blurry. With the new camera technology, we can align the frames of the movie to generate a sharper image.”

Imaging the molecule also depended on painstaking biochemical procedures, developed by Yunting Chen, PhD, an associate research scientist in the Mancia lab, to generate large quantities of the protein and separate it from the cell’s other components. “It’s a very delicate protein, and we had to mimic its environment to keep it from getting out of shape,” she says. Those efforts took about two years to perfect.

The researchers used approximately 70,000 individual pictures of STRA6 to generate a 3-dimensional map of the protein, which was used to construct an atomic model accurate to the smallest detail. The images and model revealed that STRA6 is “a bit of a freak,” says Dr. Clarke. Even more surprising was the fact that STRA6 does not work alone, but is instead tightly associated with another protein, calmodulin, which plays a key role in calcium signaling.

Although Vitamin A moves through STRA6 to enter the cell, there is no channel in STRA6 like most transporters. Instead, vitamin A enters the top of STRA6, but then appears poised to exit through a side window that opens directly into the cell membrane, not the cell interior.

Though this needs to be verified, the mechanism may be a way to protect cells from absorbing too much vitamin A. “Vitamin A is actually somewhat toxic,” says Dr. Mancia. “Trapping vitamin A inside the membrane may keep control of the amount that gets into the cell.”

The new model of STRA6 advances the understanding of a critical cellular function and may help researchers understand how other, still mysterious, cellular components work.

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The study is titled: Structure of the STRA6 receptor for retinol uptake. Additional authors include Jonathan Kim (CUMC), Sean Stowe (University of Maryland School of Medicine), Youn-Kyung Kim (Rutgers), Zahra Assur (CUMC), Michael Cavalier (University of Maryland School of Medicine), Raquel Godoy-Ruiz (University of Maryland School of Medicine), and Desiree C. von Alpen (George Washington University). Wayne Hendrickson is University Professor and the Violin Family Professor of Physiology and Cellular Biophysics.

This work was supported by an NIH-NIGMS initiative to the New York Consortium on Membrane Protein Structure (NYCOMPS; U54 GM095315) and a Charles H. Revson Senior Fellowship.

The researchers declare no conflicts of interest.

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.


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