Macroglobulin complement related (Mcr) is required for tracheal morphogenesis and septate junction function during embryogenesis and imaginal disc morphogenesis during metamorphosis. Sonia Hall, Bone Courtney, Robert Ward. Molecular Biosciences, University of Kansas, Lawrence, KS.
We isolated an allele of Macroglobulin complement related (Mcr) as a dominant modifier of br1 for leg morphogenesis during metamorphosis (prior to verifying the identify of the mutation we referred to it as sidewinder). Mcr encodes a protein with an alpha-2-macroglobulin domain and an LDL receptor A motif, and has been shown to specifically bind Candida albicans, and thus may play a role in innate immunity. Lethal phase and terminal phenotypic analyses of Mcr loss of function alleles, however, revealed that Mcr has additional essential functions during development. Mcr mutant animals are embryonic lethal with defects in cuticle deposition, tracheal tube length and diameter control, and to a lesser extent dorsal closure. This suite of phenotypes is frequently seen in mutations that affect the septate junction, an invertebrate specific junction analogous to the vertebrate tight junction. Septate junctions are indeed defective in Mcr mutant embryos as determined by the localization of the septate junction proteins Coracle, Dlg and FasIII, and by functional assays using 10 kD rhodamine dextran. RNA interference (RNAi)-based knockdown of Mcr in embryos recapitulated the loss of function phenotypes, indicating that these phenotypes are due to the specific loss of Mcr. In addition, Mcr mutations dominantly enhance the malformed leg phentopyes associated with hemizgous br1 mutation indicating a role for Mcr in imaginal disc morphogenesis. Consistent with this finding, RNAi of Mcr in leg and wing imaginal discs results in malformed legs and wings often accompanied by reduced size of the adult structures. We are currently testing whether cell growth or proliferation is also affected by loss of Mcr in imaginal discs.