Life Sciences · asia
How Are Lymphatic Vessel Growth Signals Amplified? KAIST Reveals the Structural Mechanism of Receptor Clustering
Signals that promote lymphatic vessel formation may be further amplified after receptors pair up. A South Korean research team has analyzed protein structures and identified the key to clustering between complexes. The findings offer a research direction for regulating lymphatic vessel growth, but have not yet been shown to treat lymphedema or inhibit cancer metastasis.
Lymphatic vessels collect excess fluid from tissues, and impaired drainage can cause lymphedema in the limbs. However, lymphatic vessels that proliferate around tumors may also serve as routes for cancer cells to spread. How to encourage lymphatic vessels to grow when needed and control excessive growth is an important question in research on related diseases. A South Korean research team has now identified a step that may regulate signal strength by examining how proteins are arranged on the cell surface.
On October 2, the Korea Advanced Institute of Science and Technology (KAIST) announced that a team jointly led by Ho Min Kim, a professor in its Department of Biological Sciences, and Sangkyu Lee, a researcher at the Institute for Basic Science (IBS), had resolved the structure of the growth factor VEGF-C bound to its receptor VEGFR-3. The study was published online in *Advanced Science* on September 9, focusing on how signals for lymphatic vessel formation are further amplified after receptor activation.
When VEGF-C binds to VEGFR-3 on the cell surface, it induces two receptors to pair up, transmitting signals into the cell that regulate lymphatic vessel formation and function. This pairing step has long been central to understanding receptor activation, but why signals can become stronger after pairing had not been fully clarified.
Using cryo-electron microscopy to examine the three-dimensional structure of the complexes, the team found that these complexes, which contain paired receptors, can also interlock with one another from the side to form larger clusters. KAIST's English- and Korean-language announcements both state that this arrangement reveals how the complexes cluster laterally along the cell membrane, extending the focus from a single receptor pair to contacts between multiple complexes.
Beyond structural imaging, the researchers also altered the sites where the complexes contact one another and used light to control receptor clustering, testing the relationship between their arrangement and signal strength. According to the university's announcements, these experiments support an important role for higher-order clustering in signal amplification, providing functional evidence for the observed structure.
The findings suggest a new direction for intervention: future research could explore promoting clustering to strengthen insufficient signals for lymphatic vessel formation, or inhibiting clustering to reduce excessive signals for vessel formation around tumors. However, both announcements explicitly state that the study has not demonstrated effects in treating lymphedema or inhibiting cancer metastasis. The path from understanding how proteins are arranged to determining whether this can safely improve disease outcomes still requires experimental validation.