Cells contain many types of proteins that control different aspects of cell survival, metabolism, and cell death. Each protein has a respective function at specific locations within the cell. An important job of some proteins is to generate special molecules like sugars, fats, proteins and many others. It is important that the generation of molecules like this is regulated and maintained since misregulation sometimes may lead to diseases such as cancer, Alzheimer’s disease, and many others. A class of fat molecules called phosphoinositides regulate the movement of proteins from to location to location within the cell, and help regulate cell proliferation, cell migration and much more. There are seven different phosphoinositides specific to different locations in the cell and must remain there, or else problems in cellular activity may occur. Phosphoinositides signaling is a growing field of study since their function in many aspect of cell function still poorly understood. One phosphoinositide in particular that not much is known about is called phosphatidylinositol-4-phosphate, or PI4P for short. PI4P has been reported to only be found on the cellular compartment, Golgi network, and less known is other compartments like the early endosomes. The Kenji Tanabe group from Japan may have uncovered new information about PI4P generation elsewhere in the cell, which could have important implications on cellular processes it controls.
Figure 1. The high complexity of protein networks within the cell. Image depicts colour staining the complicated network of different proteins throughout the cell and how proteins will be situated at different locations within the cell depending on cellular activity being elicited. (Image from Klingberg et al., 2014)
Kenji Tanabe and his colleges explored the dynamic activity of PI4P and how this molecule has an important function specifically at the early endosomes different from the Golgi. Early endosomes are cellular compartments important for molecule sorting in the cell, meaning that molecules are sorted to places where they need to be in the cell. They discovered the protein responsible for the production of PI4P at the early endosome is PI4KIIa. They were able to demonstrate that PI4KIIa is localized at the early endosome, and that depletion of this protein from cells decreases the production of PI4P at the early endosomes. This is the first evidence showing that PI4P is not only found at the Golgi but at different compartments of the cell. The most interesting discovery that they made was the importance of PI4P for protein movement from one location of the cell to another. Cells have receptors at the cell surface that are brought into the cell and shuttled to compartments such as the early endosomes. This is an important process for down regulating cellular signals from the receptor. If the cell is receiving too much signal from the receptor, it may be dangerous for the cells life cycle. The Tanabe lab show that depleting PI4KIIa leading to a loss of PI4P from cells did not allow receptors at the early endosome to move to different locations within the cell. This discovery has uncovered a new functional role of PI4P for receptor movement at the early endosomes.
This discovery from the Kenji Tanabe group emphasizes the importance of PI4P on cell activity especially at the early endosomes. It also proposes that PI4P production is important for receptor movement within the cell. There is evidence that functional problems in PI4K’s may lead to diseases such as tumor growth, spastic paraplegia, Gaucher’s disease and Alzheimer’s disease. With the new discovery of PI4P production on early endosomes via PI4KIIa, new drug targets become available for the development of novel inhibitors. Receptor movement is a key cellular process in cell biology. Receptors need to be moved to different places in the cell to either elicit a specific activity or even diminish its responsive signal, which control cell physiological activities like growth, movement, and survival. Often, receptor movement within the cell is misregulated in many diseases. Who knew that a molecule so small could impact such an important cellular process within the cell.
Photo Credit: Klingberg et al. (2014) J. Cell Biol. 207:283-297Published on October 20, 2014.doi: 10.1083/jcb.201402006.