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One or more keywords matched the following properties of Li, Hong-Sheng

Academic Background


B.Sc. with high honors in Biochemistry,
Wuhan University, China
Ph.D., Shanghai Brain Research Institute,
Chinese Academy of Science, China
Postdoctoral Fellow, Johns Hopkins University 1996-2001
The Albert L. Lehninger Postdoctoral Fellow Award, Johns Hopkins University 2001

Molecular Dissection of Drosophila Vision

We are using the Drosophila visual system as a genetic model to study molecular and cellular mechanisms underlying sensory functions.  By generating new fly mutants and characterizing visual phenotypes, we are investigating how photoreceptor neurons maintain their sensitivity to light and achieve rapid signaling, how visual signals are processed by interneurons, how visual glia support and modulate neuronal signaling, and how derailed signaling activities lead to neuronal degeneration in the eye.  Study on these topics will contribute to our understandings of sensory functions and neuron-glia interactions in general.  In addition, it will provide important insight to the pathology of retinitis pigmentosa and age-related macular degeneration, two human retinal disorders due to loss of photoreceptor neurons.

Using a combination of genetic, biochemical, electrophysiological, and imaging approaches, in addition to behavioral assays, we are currently focusing on the following two research directions.

Multifaceted regulation of rhodopsin in fly photoreceptors

The Drosophila visual transduction occurs in rhabdomere, a highly packed microvillar organelle in photoreceptor neurons.  Upon light-stimulated isomerization, rhodopsin triggers a trimeric Gq protein to activate phospholipase C, which leads to the open of transient-receptor-potential (TRP) channels and the depolarization of photoreceptor.  For response to repetitive stimuli, the visual transduction needs to be terminated promptly after each stimulus, which depends on deactivation of rhodopsin as well as closing of TRP channels.  Using new fly mutants, we have demonstrated that photoreceptors employ multiple mechanisms to regulate the signaling of rhodopsin, and that these regulations are important both for the speed of visual response and for the photoreceptor sensitivity to light. 

In addition to the classic, arrestin-mediated regulation, fly rhodopsin is deactivated through a mechanism that depends on a Ca2+/calmodulin-stimulated transcription factor dCAMTA.  We have identified several target genes of dCAMTA, and found that overexpression of an F-box gene dFbxl4 rescued the mutant phenotype of dCAMTA.  We will continue to investigate whether Rh1 undergoes dFbxl4-dependent ubiquitination, and whether the ubiquitination is important for Rh1 deactivation.  We have also obtained a knockout (KO) mouse line for CAMTA1, the mammalian homologue of dCAMTA, and observed similar visual defects in homozygous KO mice based on electroretinogram recordings.  Importantly, the level of mouse Fbxl4 was reduced in CAMTA1 KO mice.  Thus, the visual function of dCAMTA could be conserved from fly to mammals. 

Intriguingly, prompt deactivation of rhodopsin is also important for the maintenance of photoreceptor sensitivity.  In both dCAMTA mutant flies and a mutant lacking a visual arrestin Arr2, prolonged activation of Gq by rhodopsin triggered excessive endocytosis of the major rhodopsin Rh1 during light exposure, leading to reduced photoreceptor sensitivity to light.  In addition to the Rh1 deactivation, a CUB and LDLa domain protein (CULD) antagonizes Arr1-mediated Rh1 endocytosis for the maintenance of visual sensitivity.

As in human retinitis pigmentosa, mutations of rhodopsin and its regulatory molecules are major causes of retinal degeneration in the fly.  We have identified multiple types of retinal degeneration in fly mutants:  in older dCAMTA and arr2 mutants, excessive endocytosis of rhodopsin led to vacuolar degeneration of photoreceptor in a Ca2+-dependent manner; in a tadr (torn and diminished rhabdomeres) mutant, stimulated Gq protein failed to dissociate from the membrane and caused rhabdomere-initiated photoreceptor degeneration. These degeneration processes could also occur in human retinal disorders.

The importance of glia to visual signal transmission 

In the first visual neuropil region (lamina), fly photoreceptor axons release histamine upon light stimulation to hyperpolarize projective secondary sensory neurons and laminar local neurons. We recent found that a gap junction-dependent multicellular glial network mediates a long-distance recycling pathway of histamine for sustained visual transmission and normal visual alert response.  More importantly, we found that two ion channels in glia, Irk2 and GluCl, are essential for visual transmission in the lamina. We are currently investigating how glia receive neuronal signals through these channels and how these glial ion channels facilitate the visual transmission between photoreceptors and laminar neurons.

One or more keywords matched the following items that are connected to Li, Hong-Sheng
Item TypeName
Academic Article Coassembly of TRP and TRPL produces a distinct store-operated conductance.
Academic Article Retinal targets for calmodulin include proteins implicated in synaptic transmission.
Academic Article Assessment of the role of the inositol 1,4,5-trisphosphate receptor in the activation of transient receptor potential channels and store-operated Ca2+ entry channels.
Academic Article Requirement for the NINAC kinase/myosin for stable termination of the visual cascade.
Academic Article Termination of phototransduction requires binding of the NINAC myosin III and the PDZ protein INAD.
Academic Article TRP and the PDZ protein, INAD, form the core complex required for retention of the signalplex in Drosophila photoreceptor cells.
Academic Article Mutation of a TADR protein leads to rhodopsin and Gq-dependent retinal degeneration in Drosophila.
Academic Article A Drosophila metallophosphoesterase mediates deglycosylation of rhodopsin.
Academic Article Protein Gq modulates termination of phototransduction and prevents retinal degeneration.
Academic Article Inwardly rectifying potassium channels in Drosophila.
Academic Article A lysosomal tetraspanin associated with retinal degeneration identified via a genome-wide screen.
Academic Article The fly CAMTA transcription factor potentiates deactivation of rhodopsin, a G protein-coupled light receptor.
Academic Article A potential dimerization region of dCAMTA is critical for termination of fly visual response.
Academic Article Prolonged G(q) activity triggers fly rhodopsin endocytosis and degradation, and reduces photoreceptor sensitivity.
Academic Article Dependence on a retinophilin/myosin complex for stability of PKC and INAD and termination of phototransduction.
Concept Drosophila melanogaster
Concept Drosophila
Concept Drosophila Proteins
Academic Article Long-distance mechanism of neurotransmitter recycling mediated by glial network facilitates visual function in Drosophila.
Academic Article The putative Na?/Cl?-dependent neurotransmitter/osmolyte transporter inebriated in the Drosophila hindgut is essential for the maintenance of systemic water homeostasis.
Academic Article Loss of Na(+)/K(+)-ATPase in Drosophila photoreceptors leads to blindness and age-dependent neurodegeneration.
Academic Article Drosophila Vision Depends on Carcinine Uptake by an Organic Cation Transporter.
Search Criteria
  • Drosophila