title: The cell adhesion molecule Roughest depends on beta(Heavy)-spectrin during eye morphogenesis in Drosophila.
abstract: Cell junctions have both structural and morphogenetic roles, and contain complex mixtures of proteins whose interdependencies are still largely unknown. Junctions are also major signaling centers that signify correct integration into a tissue, and modulate cell survival. During Drosophila eye development, the activity of the immunoglobulin cell adhesion molecule Roughest (also known as Irregular chiasm C-roughest protein) mediates interommatidial cell (IOC) reorganization, leading to an apoptotic event that refines the retinal lattice. Roughest and the cadherin-based zonula adherens (ZA) are interdependent and both are modulated by the apical polarity determinant, Crumbs. Here we describe a novel relationship between the Crumbs partner beta(Heavy)-spectrin (beta(H)), the ZA and Roughest. Ectopic expression of the C-terminal segment 33 of beta(H) (betaH33) induces defects in retinal morphogenesis, resulting the preferential loss of IOC. This effect is associated with ZA disruption and Roughest displacement. In addition, loss-of-function karst and roughest mutations interact to cause a synergistic and catastrophic effect on retinal development. Finally, we show that beta(H) coimmunoprecipitates with Roughest and that the distribution of Roughest protein is disrupted in karst mutant tissue. These results suggest that the apical spectrin membrane skeleton helps to coordinate the Cadherin-based ZA with Roughest-based morphogenesis.
authors.affiliation: Department of Biology, Department of Biochemistry and Molecular Biology, Eberly College of Science, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Hyun-Gwan
authors.initials: HG
authors.lastname: Lee
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Zarnescu
authors.forename: Bryce
authors.initials: B
authors.lastname: MacIver
authors.forename: Claire M
authors.initials: CM
authors.lastname: Thomas
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000648:ultrastructure; D005123:Eye / Q000166:cytology / Q000196:embryology* / Q000648:ultrastructure; D005136:Eye Proteins / Q000378:metabolism*; D009024:Morphogenesis; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000648:ultrastructure; D011485:Protein Binding; D021381:Protein Transport; D011679:Pupa / Q000378:metabolism; D013049:Spectrin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D005136:Eye Proteins; C112961:kst protein, Drosophila; C085209:rst protein, Drosophila; D013049:Spectrin