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PMID:9888987

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Citation

Fuerstenberg, S, Peng, CY, Alvarez-Ortiz, P, Hor, T and Doe, CQ (1998) Identification of Miranda protein domains regulating asymmetric cortical localization, cargo binding, and cortical release. Mol. Cell. Neurosci. 12:325-39

Abstract

An important question in cellular and developmental biology is how a cell divides to produce daughter cells with different fates. Drosophila neuroblasts are a model system for studying asymmetric cell division: at each division, neuroblasts retain stem cell-like features, whereas their sibling ganglion mother cell (GMC) has a more restricted fate. Establishing neuroblast/GMC differences involves the asymmetric localization of proteins (Inscuteable, Miranda, Prospero, and Staufen) and RNA (prospero). All of these factors are apically localized during interphase, and all except Inscuteable move to the basal cortex at mitosis prior to being partitioned solely into the GMC. In this study, we show that Miranda is colocalized with Staufen and Prospero in neuroblasts, and is required for the asymmetric cortical localization of both proteins. Analysis of miranda mutants reveals three functional domains within the Miranda protein: (1) an N-terminal domain (1-290 aa) sufficient for association of Miranda with the cell cortex and basal localization in mitotic neuroblasts; (2) a central domain (446-727 aa) necessary for apical localization in interphase neuroblasts as well as for "cargo binding" of Prospero, Staufen, and prospero mRNA; and (3) a C-terminal domain (727-830 aa) necessary for the timely degradation of Miranda and release of its cargo from the cortex of the newborn GMC. In addition, Miranda is asymmetrically localized in epithelial cells that lack Inscuteable and divide symmetrically; thus the mechanism regulating Miranda localization is common to epithelial cells and neuroblasts, and Inscuteable is not an obligate component. Finally, we define a C-terminal domain of Staufen sufficient for Miranda-dependent cortical localization in neuroblasts.

Links

PubMed Online version:10.1006/mcne.1998.0724

Keywords

Amino Acid Sequence; Animals; Binding Sites/physiology; Brain Chemistry; Cell Cycle Proteins/chemistry; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; Drosophila; Drosophila Proteins; Epithelial Cells/chemistry; Epithelial Cells/cytology; Ganglia, Invertebrate/chemistry; Ganglia, Invertebrate/cytology; Gene Expression/physiology; Insect Proteins/analysis; Insect Proteins/chemistry; Interphase/physiology; Molecular Sequence Data; Mutation; Nerve Tissue Proteins/chemistry; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neurons/chemistry; Neurons/cytology; Nuclear Proteins/chemistry; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Protein Structure, Secondary; Protein Structure, Tertiary; RNA-Binding Proteins/chemistry; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism; Stem Cells/chemistry; Stem Cells/cytology; Transcription Factors/chemistry; Transcription Factors/genetics; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:STAU

located_in

GO:0045180: basal cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:STAU

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:STAU

located_in

GO:0045177: apical part of cell

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:PROS

located_in

GO:0045180: basal cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q24367

located_in

GO:0045179: apical cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q5BIH3

located_in

GO:0045179: apical cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q94543

located_in

GO:0045179: apical cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q9VDR7

involved_in

GO:0030162: regulation of proteolysis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VDR7

located_in

GO:0045180: basal cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q9VDR7

located_in

GO:0045177: apical part of cell

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q9VDR7

involved_in

GO:0045167: asymmetric protein localization involved in cell fate determination

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9W2R4

located_in

GO:0045179: apical cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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