TRP gating is linked to the metabolic state and maintenance of the Drosophila photoreceptor cells.
The Drosophila light-activated channel TRP is the founding member of a large and diverse family of channel proteins that is conserved throughout evolution. In spite of much progress, the gating mechanism of TRP channels is still unknown. However, recent studies have shown multi-faceted functions of the Drosophila light-sensitive TRP channel that may shed light on TRP gating. Accordingly, metabolic stress, which leads to depletion of cellular ATP, reversibly activates the Drosophila TRP and TRPL channels in the dark in a constitutive manner. In several Drosophila mutants, constitutive activity of TRP channels lead to a rapid retinal degeneration in the dark, while genetic elimination of TRP protects the cells from degeneration. Additional studies have shown that TRPL translocates in a light-dependent manner between the signaling membranes and the cell body. This light-activated translocation is accompanied by reversible morphological changes leading to partial and reversible collapse of the microvillar signaling membranes into the cytosol, which allows turnover of signaling molecules. These morphological changes are also blocked by genetic elimination of TRP channels. The link of TRP gating to the metabolic state and maintenance of cells makes cells expressing TRP extremely vulnerable to metabolic stress via a mechanism that may underlie retinal degeneration and neuronal cell death upon malfunction.
Minke
Baruch
B
Department of Physiology, Kühne Minerva Center for Studies of Visual Transduction, Hadassah Medical School, The Hebrew University, P.O. Box 12272, Jerusalem 91120, Israel. minke@md.huji.ac.il
Agam
Keren
K
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D002148:Calmodulin-Binding Proteins / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000378:metabolism; D015640:Ion Channel Gating; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017956:Photoreceptor Cells, Invertebrate / Q000737:chemistry / Q000502:physiology; D050051:Transient Receptor Potential Channels; D014785:Vision, Ocular / Q000502:physiology*
D015220:Calcium Channels; D002148:Calmodulin-Binding Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D050051:Transient Receptor Potential Channels; C063169:trp protein, Drosophila; C074192:trpl protein, Drosophila