Linked Life Data

20592197

Source:http://linkedlifedata.com/resource/pubmed/id/20592197

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2010-7-1
pubmed:abstractText
Vertebrate photoreceptors have a modified cilium composed of a basal body, axoneme and outer segment. The outer segment includes stacked membrane discs, containing opsin and the signal transduction apparatus mediating phototransduction. In photoreceptors, two distinct classes of vesicles are trafficked. Synaptic vesicles are transported down the axon to the synapse, whereas opsin-containing vesicles are transported to the outer segment. The continuous replacement of the outer segments imposes a significant biosynthetic and trafficking burden on the photoreceptors. Here, we show that Ahi1, a gene that when mutated results in the neurodevelopmental disorder, Joubert syndrome (JBTS), is required for photoreceptor sensory cilia formation and the development of photoreceptor outer segments. In mice with a targeted deletion of Ahi1, photoreceptors undergo early degeneration. Whereas synaptic proteins are correctly trafficked, photoreceptor outer segment proteins fail to be transported appropriately or are significantly reduced in their expression levels (i.e., transducin and Rom1) in Ahi1(-/-) mice. We show that vesicular targeting defects in Ahi1(-/-) mice are cilium specific, and our evidence suggests that the defects are caused by a decrease in expression of the small GTPase Rab8a, a protein required for accurate polarized vesicular trafficking. Thus, our results suggest that Ahi1 plays a role in stabilizing the outer segment proteins, transducin and Rom1, and that Ahi1 is an important component of Rab8a-mediated vesicular trafficking in photoreceptors. The retinal degeneration observed in Ahi1(-/-) mice recapitulates aspects of the retinal phenotype observed in patients with JBTS and suggests the importance of Ahi1 in photoreceptor function.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
30
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8759-68
pubmed:dateRevised
2011-6-13
pubmed:meshHeading
pubmed-meshheading:20592197-Animals, pubmed-meshheading:20592197-Brain Diseases, pubmed-meshheading:20592197-Cilia, pubmed-meshheading:20592197-Eye Proteins, pubmed-meshheading:20592197-GTP-Binding Protein alpha Subunits, pubmed-meshheading:20592197-Gene Deletion, pubmed-meshheading:20592197-Membrane Proteins, pubmed-meshheading:20592197-Mice, pubmed-meshheading:20592197-Mice, Inbred BALB C, pubmed-meshheading:20592197-Mice, Knockout, pubmed-meshheading:20592197-Proto-Oncogene Proteins, pubmed-meshheading:20592197-Retina, pubmed-meshheading:20592197-Retinal Degeneration, pubmed-meshheading:20592197-Retinal Photoreceptor Cell Outer Segment, pubmed-meshheading:20592197-Synaptic Vesicles, pubmed-meshheading:20592197-Syndrome, pubmed-meshheading:20592197-Transducin, pubmed-meshheading:20592197-rab GTP-Binding Proteins
pubmed:year
2010
pubmed:articleTitle
Retinal degeneration and failure of photoreceptor outer segment formation in mice with targeted deletion of the Joubert syndrome gene, Ahi1.
pubmed:affiliation
Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural