Moesin is critical for rhabdomere morphogenesis in the developing Drosophila retina
Abstract
Coordinated local reorganization of the cytoskeleton and directed membrane transport to restricted regions of the cell surface drives epithelial differentiation. Morphogenesis of the Drosophila rhabdomere, the photosensitive membrane organelle of compound eye photoreceptors, offers an attractive model system for investigating membrane-cytoskeleton interactions during development. Photosensory membranes, the outer segments of vertebrate rod and cone photoreceptors and the rhabdomeres of arthropods, are exaggerated products of a common program of epithelial differentiation: apical membrane expansion and specialization. How this coordination is effected is not understood. Ezrin-Radixin-Moesin (ERM) family proteins that organize heterogeneous sub-membrane protein scaffolds that shape membranes and their physiology are attractive candidates to orchestrate complex cellular processes such as morphogenesis. I investigated the role of the single Drosophila ERM homolog Moesin in rhabdomere morphogenesis with a combination of cellular, molecular and genetic approaches and found that it is crucial for photoreceptor morphogenesis. Moesin localizes to the interface between the photosensory membrane and photoreceptor cytoplasm generally, a dynamic locus of membrane addition and cytoskeletal reorganization. Down-regulation of Moesin via RNA interference or dominant-negative Moesin expression during photoreceptor terminal differentiation disrupts the apical cytoskeleton and the vesicle traffic that builds the sensory membrane. Over-expression of constitutively active Moesin prevents regionalization of the photoreceptor apical membrane. High concentrations of the small GTPase Rho and Protein Kinase C (PKC) localize to the sensory compartment, and manipulations of Rho and PKC abolish Moesin phosphorylation, providing a pathway for photoreceptor Moesin activation. These results suggest Moesin coordinates photoreceptor morphogenesis via its dual ability to link the plasma membrane to the cytoskeleton and to localize regulators of small GTPase signaling.
Degree
Ph.D.
Advisors
Ready, Purdue University.
Subject Area
Cellular biology
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