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Neuroscience and Neurobiology

Animals, Genetically Modified

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Animal Cryptochromes Mediate Magnetoreception By An Unconventional Photochemical Mechanism, Robert Gegear, Lauren Foley, Amy Casselman, Steven Reppert Dec 2015

Animal Cryptochromes Mediate Magnetoreception By An Unconventional Photochemical Mechanism, Robert Gegear, Lauren Foley, Amy Casselman, Steven Reppert

Robert J. Gegear

Understanding the biophysical basis of animal magnetoreception has been one of the greatest challenges in sensory biology. Recently it was discovered that the light-dependent magnetic sense of Drosophila melanogaster is mediated by the ultraviolet (UV)-A/blue light photoreceptor cryptochrome (Cry). Here we show, using a transgenic approach, that the photoreceptive, Drosophila-like type 1 Cry and the transcriptionally repressive, vertebrate-like type 2 Cry of the monarch butterfly (Danaus plexippus) can both function in the magnetoreception system of Drosophila and require UV-A/blue light (wavelength below 420 nm) to do so. The lack of magnetic responses for both Cry types at wavelengths above 420 …


Human Cryptochrome Exhibits Light-Dependent Magnetosensitivity, Lauren Foley, Robert Gegear, Steven Reppert Dec 2015

Human Cryptochrome Exhibits Light-Dependent Magnetosensitivity, Lauren Foley, Robert Gegear, Steven Reppert

Robert J. Gegear

Humans are not believed to have a magnetic sense, even though many animals use the Earth's magnetic field for orientation and navigation. One model of magnetosensing in animals proposes that geomagnetic fields are perceived by light-sensitive chemical reactions involving the flavoprotein cryptochrome (CRY). Here we show using a transgenic approach that human CRY2, which is heavily expressed in the retina, can function as a magnetosensor in the magnetoreception system of Drosophila and that it does so in a light-dependent manner. The results show that human CRY2 has the molecular capability to function as a light-sensitive magnetosensor and reopen an area …


Protein Gq Modulates Termination Of Phototransduction And Prevents Retinal Degeneration, Wen Hu, Didi Wan, Xiaoming Yu, Jinguo Cao, Peiyi Guo, Hong-Sheng Li, Junhai Han Jul 2015

Protein Gq Modulates Termination Of Phototransduction And Prevents Retinal Degeneration, Wen Hu, Didi Wan, Xiaoming Yu, Jinguo Cao, Peiyi Guo, Hong-Sheng Li, Junhai Han

Peiyi Guo

Appropriate termination of the phototransduction cascade is critical for photoreceptors to achieve high temporal resolution and to prevent excessive Ca(2+)-induced cell toxicity. Using a genetic screen to identify defective photoresponse mutants in Drosophila, we isolated and identified a novel Galpha(q) mutant allele, which has defects in both activation and deactivation. We revealed that G(q) modulates the termination of the light response and that metarhodopsin/G(q) interaction affects subsequent arrestin-rhodopsin (Arr2-Rh1) binding, which mediates the deactivation of metarhodopsin. We further showed that the Galpha(q) mutant undergoes light-dependent retinal degeneration, which is due to the slow accumulation of stable Arr2-Rh1 complexes. Our study …


Dsarm/Sarm1 Is Required For Activation Of An Injury-Induced Axon Death Pathway, Jeannette Osterloh, Jing Yang, Timothy Rooney, A. Fox, Robert Adalbert, Eric Powell, Amy Sheehan, Michelle Avery, Rachel Hackett, Mary Logan, Jennifer Macdonald, Jennifer Ziegenfuss, Stefan Milde, Ying-Ju Hou, Carl Nathan, Aihao Ding, Robert Brown, Laura Comforti, Michael Coleman, Marc Tessier-Lavigne, Stephan Zuchner, Marc Freeman Dec 2012

Dsarm/Sarm1 Is Required For Activation Of An Injury-Induced Axon Death Pathway, Jeannette Osterloh, Jing Yang, Timothy Rooney, A. Fox, Robert Adalbert, Eric Powell, Amy Sheehan, Michelle Avery, Rachel Hackett, Mary Logan, Jennifer Macdonald, Jennifer Ziegenfuss, Stefan Milde, Ying-Ju Hou, Carl Nathan, Aihao Ding, Robert Brown, Laura Comforti, Michael Coleman, Marc Tessier-Lavigne, Stephan Zuchner, Marc Freeman

Dr Robert Brown

Axonal and synaptic degeneration is a hallmark of peripheral neuropathy, brain injury, and neurodegenerative disease. Axonal degeneration has been proposed to be mediated by an active autodestruction program, akin to apoptotic cell death; however, loss-of-function mutations capable of potently blocking axon self-destruction have not been described. Here, we show that loss of the Drosophila Toll receptor adaptor dSarm (sterile alpha/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously suppresses Wallerian degeneration for weeks after axotomy. Severed mouse Sarm1 null axons exhibit remarkable long-term survival both in vivo and in vitro, indicating that Sarm1 prodegenerative signaling is conserved in mammals. Our results provide direct …