Â鶹´«Ã½

News — DALLAS – April 09, 2025 – Using a novel method that gives a readout of which proteins are in specific locations within cells, UT Southwestern Medical Center researchers have identified a protein that plays a key role in cell adhesion and movement. Their findings, published in , could help researchers better understand diverse phenomena such as cancer metastasis and cell differentiation.

“Our lab has a longstanding interest in understanding how cells are spatially organized. This work developed a new biochemical method that uncovered the function of a poorly characterized protein called calmin,” said , Associate Professor of  and  and a member of the  at UT Southwestern. He co-led the study with first author Holly Merta, Ph.D., a postdoctoral researcher in the .

Dr. Merta explained that she, Dr. Henne, and their colleagues were originally interested in better understanding how proteins are organized in the endoplasmic reticulum (ER), a cellular organelle with a broad range of functions including storing calcium, synthesizing some lipids and cholesterol, and transporting proteins to other cellular locations. Because the proteins performing these functions are thought to be organized into discrete locations within the ER, the researchers wanted to learn which proteins are found within these different locations.

To do this, they developed an approach called sub-organelle spatial proteomics by combining the gene editing tool CRISPR with TurboID, an enzyme that adds a chemical tag onto all proteins that are in close proximity. These tagged proteins can then be isolated and identified. By strategically anchoring TurboID onto different proteins known to localize in specific regions of the cell interior, researchers can create a “map” of the protein landscape.

The researchers fused TurboID to four proteins known to be in different subregions of the ER, then worked with UTSW’s  to identify all the tagged proteins. When they examined which proteins were located in the ER’s membrane tubules, they were surprised to find calmin, a protein whose function was previously unknown.

A closer look showed calmin appeared to bind to F-actin, a protein that’s part of the cytoskeleton – a network of fibers that helps cells hold their shape, move, and connect with surfaces through sticky junctions called focal adhesions. When the researchers used a genetic trick to deplete calmin in motile cells, the cells moved significantly slower and developed more focal adhesions. Causing cells to overproduce calmin had the opposite effect.

Together, these findings suggested calmin is necessary to break down the F-actin fibers responsible for stabilizing focal adhesions, increasing adhesion turnover. Further experiments suggest calmin does this by increasing molecular signaling that relies on calcium stored in the ER.

Because calmin is often mutated in cancers, Drs. Henne and Merta said this protein may be pivotal for metastasis, the spread of cancer cells beyond the original tumor. Increasing focal adhesions could help metastatic cells survive in their new anatomical locations, establishing secondary tumors. Calmin has also been identified in developing neurons, where it may be important for growing the long extensions characteristic of these cells. The researchers plan to investigate these possibilities in future studies.

Other UTSW scientists who contributed to this study include Gaudenz Danuser, Ph.D., Chair and Professor of the  and Professor of Cell Biology; Arun Radhakrishnan, Ph.D., Professor of ; Tadamoto Isogai, Ph.D., Assistant Professor in the Lyda Hill Department of Bioinformatics; Achinta Sannigrahi, Ph.D., postdoctoral researcher; and Kaitlynn Gov, B.S., graduate student researcher.

Dr. Henne holds the Martha Lee Foster Professorship in Brain Science and Medicine and is a W. W. Caruth, Jr. Scholar in Biomedical Research.

This study was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK126887), the National Institute of General Medical Sciences (GM119768 and GM145399), the National Institutes of Health (HL160487, AI158357, T32 DK007307, F32 GM154450, and 1S10OD028630-01); The Welch Foundation (I-1873 and I-1793), the UT Southwestern Medical Center Endowed Scholars Program, the Leducq Foundation (19CVD04), and a National Cancer Institute (NCI) Cancer Center Support Grant (P30CA142543).

About UT Southwestern Medical Center   

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.