Highlight Publication October 2010

Georgiev P, Okkenhaug H, Drews A, Wright D, Lambert S, Flick M, Carta V, Martel C, Oberwinkler J, Padinjat R
TRPM channels mediate zinc homeostasis and cellular growth during Drosophila larval development.
Cell Metabolism
http://dx.doi.org/10.1016/j.cmet.2010.08.012
(R Padinjat is cited as P Raghu)

Lay description

Ion channels are protein molecules that control the movement of elemental ions such as sodium, potassium and calcium in and out of cells. There is a huge diversity of ion channels that regulate cell function; one class of these are members of the TRP superfamily of ion channels. TRP channels have generally been implicated in the detection and interpretation of environmental changes by cells and are usually regulators of sodium and calcium influx. In this paper Georgiev et al find that one subset of TRP channels, TRPM, in the fruitfly Drosophila primarily controls the levels of the trace metal Zinc. They find that this function of TRPM channels is required to support cell growth during development.

The experiments now reported reveal that TRPM deficiency in Drosophila leads to a profound reduction in larval growth resulting from a decrease in cell size and associated defects in mitochondrial structure and function: mitochondria were aberrantly fused to form long tubular structures and levels of ATP, a key chemical energy source produced by mitochondria, were reduced. This reduction in ATP levels strongly suggests that the cellular growth defect in TRPM-deficient larvae is underpinned by a major deficit in the cellular energy supply required to undertake protein biosynthesis. These findings are also consistent with embryonic growth defects reported in mice lacking the gene encoding a Zinc transporter protein.

Regulation of Zinc levels has been implicated in a number of medical conditions including neurodegenerative diseases. The work reported in this paper is likely to have implications for the understanding of how Zinc levels are regulated by mammalian TRPM channels of biomedical relevance

About the lead author

Plamen Georgiev obtained his M.Sc. in Molecular biology with specialization in Genetics from Sofia University, Bulgaria, following his work at the Bulgarian Academy of Sciences on the role of histamine-gated chloride channels in Drosophila photoreceptor synaptic transmission. He then joined Dr Raghu Padinjat’s lab in the Department of Anatomy, Cambridge University, as a research assistant to study the mechanisms of Drosophila TRPC channel activation and retinal degeneration.

As a PhD student in the Padinjat lab at the Babraham Institute, Plamen was involved in the characterization of a novel Drosophila gene encoding a putative TRPM ion channel and successfully obtained his degree in 2007. He continued his postdoctoral research in Raghu’s lab before recently joining the Max-Planck Institute of Immunobiology, Freiburg, Germany, as a manager of their Fly Facility and also carrying out research in Dr Asifa Akhtar’s Laboratory of Chromatin Regulation.