The ‘lipid raft’ microdomain proteins Reggie-1 and Reggie-2 (flotillins) are scaffolds for protein interaction and signalling

Department of Biology, University of Konstanz, 78467 Konstanz, Germany.
Biochemical Society Symposium (Impact Factor: 3.38). 02/2005; 72(72):109-18. DOI: 10.1042/bss0720109
Source: PubMed


Reggie-1 and reggie-2 are two evolutionarily highly conserved proteins which are up-regulated in retinal ganglion cells during regeneration of lesioned axons in the goldfish optic nerve. They are located at the cytoplasmic face of the plasma membrane and are considered to be 'lipid raft' constituents due to their insolubility in Triton X-100 and presence in the 'floating fractions'; hence they were independently named flotillins. According to our current view, the reggies subserve functions as protein scaffolds which form microdomains in neurons, lymphocytes and many other cell types across species as distant as flies and humans. These microdomains are of a surprisingly constant size of less than or equal to 0.1 mm in all cell types, whereas the distance between them is variable. The microdomains co-ordinate signal transduction of specific cell-surface proteins and especially of GPI (glycosylphosphatidylinositol)-anchored proteins into the cell, as is demonstrated for PrP(c) (cellular prion protein) in T-lymphocytes. These cells possess a pre-formed reggie cap scaffold consisting of densely packed reggie microdomains. PrP(c) is targeted to the lymphocyte reggie cap when activated by antibody cross-linking, and induces a distinct Ca(2+) signal. In developing zebrafish, reggies become concentrated in neurons and axon tracts, and their absence, after morpholino antisense RNA-knockdown, results in deformed embryos with reduced brains. Likewise, defects in Drosophila eye morphogenesis occur upon reggie overexpression in mutant flies. The defects observed in the organism, as well as in single cells in culture, indicate a morphogenetic function of the reggies, with emphasis on the nervous system. This complies with their role as scaffolds for the formation of multiprotein complexes involved in signalling across the plasma membrane.

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    • "Flo-2 is expressed predominantly in neuronal structures such as the optic lobes and the central brain during all developmental stages of D. melanogaster [26]. Overexpression of Flo-2 leads to detrimental effects during the development of eyes, ocelli, bristles, and wings [27], while knockout mutants surprisingly show no noticeable phenotypic abnormalities. As Flo-2 covers almost the entire genomic section of the candidate region we will refer to it as the ‘Flo-2 region’. "
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    • "The microdomains appear as dots or puncta at the plasma membrane of cells and along axons, growth cones, filopodia and as densely packed rows of dots, for instance, at cell–cell contacts [21] [22] and in the T cell cap [20] [23]. This " pearl on a string-like " arrangement in T cell caps and at cell contacts (Fig. 2) is formed by a reduction of the distance between individual microdomains [22]. Fig. 1. "
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