黑料吃瓜资源

Many cells are covered with mysterious large holes, pores that have been associated with the sense of taste as well as Alzheimer鈥檚 disease, depression, and even asthma. Knowing the structure of these varied holes will help researchers better understand this range of associations and provide a blueprint for developing new therapies.

鈥淥ne of the most recently discovered of these 鈥榣arge holes鈥� are called calcium homeostasis modulators (CALHMs),鈥� said 黑料吃瓜资源 Professor Furukawa. 鈥淭hey鈥檙e basically pores on the surface of some cells such as neurons,鈥� that let various molecules enter and exit the cell.

As described recently in Nature Structural & Molecular Biology, researchers from Furukawa鈥檚 lab showcased the detailed structure of two CALHMs and how they function.

鈥淚f you have large holes in cells, you鈥檇 think the cells would burst open or shrink,鈥� said Johanna Syrjanen, a postdoctoral researcher who helped lead the research. However, she added, cells with functioning pores 鈥渞emain quite happily as they are.鈥�

That suggests these pores are important for maintaining cell health. To investigate this, the researchers studied two kinds of pores. The pore CALHM1 is involved in sensing bitter or sweet tastes, and even that savory fifth taste known as umami. This pore is also involved in controlling the airways in your lungs, which implicates it in asthma. Additionally, mutations in the genes that shape CALHM1 have been associated with Alzheimer鈥檚 disease. The researchers also studied another pore, CALHM2 that might be involved in depression. To their surprise, they found that CALHM2 has much larger pore size compared to CALHM1.

鈥淧resumably the opening and closing of these pores is tightly regulated in some way,鈥� said Syrjanen. This opening and closing might be key to how the pores influence taste or are associated with disease. To make sense of this, 鈥渨e first have to be able to visualize them and use that information as a guide for further experiments,鈥� she explained.

To visualize the structure of CALHM1 and CALHM2, Furukawa鈥檚 lab used cryo-electron microscopy, which fires a powerful electron through a rapidly frozen specimen to obtain images. They then carefully compound the images in various orientations into a 3-D model that highlights the finite details of each pore鈥檚 structure.

鈥淲e鈥檝e provided science with the first blueprint of these pores to design therapeutic compounds,鈥� said Furukawa. 鈥淭he hope is that such compounds could be effective in treating diseases and disorders like Alzheimer鈥檚 and depression, and potentially in asthma.鈥�

Written by: Brian Stallard, Content Developer/Communicator | [email protected] | 516-367-8455

Funding

This work was supported by the National Institutes of Health (NIH), the Robertson funds at 黑料吃瓜资源, the Doug Fox Alzheimer鈥檚 fund, Austin鈥檚 purpose, and Heartfelt Wing Alzheimer鈥檚 fund. Johanna Syrjanen is a Charles H. Revson Senior Fellow in Biomedical Science.

Citation

Syrjanen et al, 鈥淪tructure and assembly of calcium homeostasis modulator proteins,鈥� Nature Structural and Molecular Biology, 27 Jan 2020