PUBLICATION
Multiple domains in the Crumbs Homolog 2a (Crb2a) protein are required for regulating rod photoreceptor size
- Authors
- Hsu, Y.C., and Jensen, A.M.
- ID
- ZDB-PUB-100806-1
- Date
- 2010
- Source
- BMC Cell Biology 11: 60 (Journal)
- Registered Authors
- Jensen, Abigail
- Keywords
- none
- MeSH Terms
-
- Adherens Junctions/genetics
- Adherens Junctions/metabolism*
- Animals
- Animals, Genetically Modified
- Cell Polarity/genetics
- Cell Size
- Eye/embryology
- Eye/growth & development*
- Eye/pathology
- Humans
- Membrane Proteins/genetics
- Membrane Proteins/metabolism
- Morphogenesis/genetics
- Protein Engineering
- Protein Structure, Tertiary/genetics
- Protein Transport/genetics
- Rod Cell Outer Segment/metabolism*
- Rod Cell Outer Segment/pathology
- Sequence Deletion/genetics
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 20670434 Full text @ BMC Cell Biol.
Citation
Hsu, Y.C., and Jensen, A.M. (2010) Multiple domains in the Crumbs Homolog 2a (Crb2a) protein are required for regulating rod photoreceptor size. BMC Cell Biology. 11:60.
Abstract
BACKGROUND: Vertebrate retinal photoreceptors are morphologically complex cells that have two apical regions, the inner segment and the outer segment. The outer segment is a modified cilium and is continuously regenerated throughout the life of the organism. The molecular and cellular mechanisms that underlie vertebrate photoreceptor morphogenesis and the maintenance of the outer segment are largely unknown. The Crumbs (Crb) complex is a key regulator of apical membrane identity and size in epithelia and Drosophila photoreceptors. Mutations in the human gene CRUMBS HOMOLOG 1 (CRB1) are associated with early and severe vision loss. Drosophila Crumbs and vertebrate Crb1 and Crumbs homolog 2 (Crb2) proteins are similar structurally, all are single pass transmembrane proteins with a large extracellular domain containing multiple laminin- and EGF-like repeats and a small intracellular domain containing a FERM-binding domain and a PDZ-binding domain. In order to begin to understand the role of the Crb family of proteins in vertebrate photoreceptors we generated stable transgenic zebrafish in which rod photoreceptors overexpress full-length Crb2a protein and several other Crb2a constructs engineered to lack specific domains. RESULTS: We examined the localization of Crb2a constructs and their effects on rod morphology. We found that only the full-length Crb2a protein approximated the normal localization of Crb2a protein apical to adherens junctions in the photoreceptor inner segment. Several Crb2a construct proteins localized abnormally to the outer segment and one construct localized abnormally to the cell body. Overexpression of full-length Crb2a greatly increased inner segment size while expression of several other constructs increased outer segment size. CONCLUSIONS: Our observations suggest that particular domains in Crb2a regulate its localization and thus may regulate its regionalized function. Our results also suggest that the PDZ-binding domain in Crb2a might bring a protein(s) into the Crb complex that alters the function of the FERM-binding domain.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping