It gives us great pleasure to see a substantial and complex line of research enquiry be recognised via publication in the prestigious journal Developmental Cell. CHIRI’s Carl Mousley is a leading author in an international collaborative study shedding light on functional proteins that are critical in regulation of cell proliferation and by extension, potential target for cancer treatment. Have a read of the study and please take the opportunity to congratulate Carl on this outstanding achievement.
How do cells decide to grow or not? Cells proliferate, or grow, when they are told to do so. These instructions are provided in the form of nutrients or growth signals termed growth factors. Cells must interpret these cues and mount an appropriate growth response. The converse is also true; nutrient starvation or growth inhibitory signals can stop cell growth or induce ‘quiescence’. Understanding how cells read and respond to these signals to either proliferate or quiesce is an important question in cell biology, particularly as these processes are found to be dysfunctional in many forms of cancer.
For a cell to grow they must transport new material, in the form of proteins and lipids, from inside to the cell periphery or plasma membrane. This process is known as membrane trafficking or vesicular transport and is also the process used by cells to secrete important proteins such as antibodies. This process requires the function of several internal cellular compartments, or organelles, that as a whole are referred to as the secretory pathway. We were interested to investigate whether the central sorting station of the secretory pathway known as the Golgi apparatus can instruct cells to grow or not. Golgi function is regulated by the opposing activity of two different lipid binding proteins; a Phosphatidylinositol transfer protein (PITP) promotes transport from the Golgi whereas an oxysterol binding protein homologue (Osh4) inhibits transport. Our research has identified a new role for these proteins in regulating cell proliferation in addition to their well characterised roles in regulating protein transport. PITP function is required to instruct cells to initiate a new round of cell growth. In contrast, Osh4 function instructs cells to stop proliferation and become quiescent. Furthermore, we find that cells negatively regulate the activity of Osh4 by a protein modification known as acetylation when nutrients are plentiful to prevent growth arrest. In the future we hope to investigate whether Osh proteins define a family of stage-specific cell-cycle control factors that execute tumour-suppressor-like functions.
