Miranda as a multidomain adapter linking apically localized Inscuteable and basally localized Staufen and Prospero during asymmetric cell division in Drosophila.
Neuroblasts in the developing Drosophila CNS asymmetrically localize the cell fate determinants Numb and Prospero as well as prospero RNA to the basal cortex during mitosis. The localization of Prospero requires the function of inscuteable and miranda, whereas prospero RNA localization requires inscuteable and staufen function. We demonstrate that Miranda contains multiple functional domains: an amino-terminal asymmetric localization domain, which interacts with Inscuteable, a central Numb interaction domain, and a more carboxy-terminal Prospero interaction domain. We also show that Miranda and Staufen have similar subcellular localization patterns and interact in vitro. Furthermore, miranda function is required for the asymmetric localization of Staufen. Miranda localization is disrupted by the microfilament disrupting agent latrunculin A. Our results suggest that Miranda directs the basal cortical localization of multiple molecules, including Staufen and prospero RNA, in mitotic neuroblasts in an actin-dependent manner.
Shen
C P
CP
Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco, San Francisco, California 94143-0725 USA.
Knoblich
J A
JA
Chan
Y M
YM
Jiang
M M
MM
Jan
L Y
LY
Jan
Y N
YN
D000199:Actins / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002490:Central Nervous System / Q000737:chemistry / Q000166:cytology / Q000196:embryology; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D004330:Drosophila / Q000737:chemistry / Q000166:cytology* / Q000196:embryology; D029721:Drosophila Proteins; D015870:Gene Expression / Q000235:genetics; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D007605:Juvenile Hormones / Q000502:physiology; D008297:Male; D008938:Mitosis; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D009479:Neuropeptides; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D010446:Peptide Fragments / Q000737:chemistry; D017434:Protein Structure, Tertiary; D012313:RNA / Q000032:analysis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors
D000199:Actins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D007605:Juvenile Hormones; C107613:Mira protein, Drosophila; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C098678:insc protein, Drosophila; C060606:numb protein, Drosophila; C073099:pros protein, Drosophila; C069927:stau protein, Drosophila; D012313:RNA