Disease relevance of insc

• The most upstream component identified so far which acts to organise both neuroblast and ganglion mother cell asymmetric divisions is encoded by inscuteable [1].

High impact information on insc

• The Partner of Inscuteable/Discs-large complex is required to establish planar polarity during asymmetric cell division in Drosophila [2].
• We demonstrate that prospero RNA is also asymmetrically localized and partitioned during neuroblast cell divisions, a process requiring both inscuteable and staufen [3].
• Hence staufen also acts zygotically, downstream of inscuteable, to effect aspects of neuroblast asymmetry [3].
• The asymmetric localization of Miranda protein requires inscuteable [4].
• Our findings link cdc2 with asymmetric divisions, and explain why the asymmetric localization of molecules like Inscuteable show cell-cycle dependence [5].

Biological context of insc

• We conclude that localization of insc mRNA transcripts in neuroblasts confers maximal levels of apical Insc activity, which is required for accurate control of metaphase spindle length, division orientation, and asymmetric cell division [6].
• Our results demonstrate a novel role for Abs in the posttranscriptional regulation of insc expression, which is essential for proper cell polarity, spindle orientation, and the establishment of distinct sibling cell fates within embryonic neural and muscle progenitors [7].
• In neuroblasts we observe loss of apical Insc crescents, failure in basal protein targeting, and defects in spindle orientation [7].
• The Mira/Pros telophase rescue seen in inscuteable mutant NBs requires DTRAF1 [8].
• Although localisation of Inscuteable in pins mutants was initiated correctly during neuroblast delamination, Inscuteable became homogeneously distributed in the cytoplasm during mitosis [9].

Anatomical context of insc

• When neuroblasts divide, inscuteable acts to coordinate protein localization and mitotic spindle orientation, ensuring that asymmetrically localized determinants like Prospero partition into one progeny. staufen encodes a dsRNA-binding protein implicated in mRNA transport in oocytes [3].
• Moreover, ectopic expression of inscuteable in other epithelial cells leads to spindle reorientation [10].
• Our results suggest that miranda functions downstream of inscuteable and works as an adapter that connects Prospero to the basal cell membrane during asymmetric cell division [4].
• Loss of numb or inscuteable results in opposite cell fate transformations-both prevent sibling myoblasts from adopting distinct identities, resulting in duplicated or deleted mesodermal structures [11].
• Binary sibling neuronal cell fate decisions in the Drosophila embryonic central nervous system are nonstochastic and require inscuteable-mediated asymmetry of ganglion mother cells [12].

Associations of insc with chemical compounds

• Bazooka provides an apical cue for Inscuteable localization in Drosophila neuroblasts [13].
• In this study, we have used a simple Ca(2+) imaging assay to compare the abilities of various Ins (1,4,5)P(3)-metabolizing enzymes to regulate a maximal histamine-stimulated Ca(2+) signal in HeLa cells [14].

Physical interactions of insc

• Furthermore, we find that the Abs protein physically interacts with insc RNA [7].
• Asymmetric localisation of Inscuteable is initiated during neuroblast delamination by direct binding to Bazooka, an apically localised protein that contains protein-interaction motifs known as PDZ domains [9].

Regulatory relationships of insc

• The Snail protein family regulates neuroblast expression of inscuteable and string, genes involved in asymmetry and cell division in Drosophila [15].

Other interactions of insc

• Abstrakt, a DEAD box protein, regulates Insc levels and asymmetric division of neural and mesodermal progenitors [7].
• Furthermore, in insc mutants the eve expressing pericardial cells of the developing heart are significantly reduced in numbers [16].
• Inscuteable (Insc) and Partner of Inscuteable (Pins) are translocated to the apical cell cortex during asymmetrical cell division of Drosophila neuroblast [17].
• BACKGROUND: In the fruit fly Drosophila, the Inscuteable protein localises to the apical cell cortex in neuroblasts and directs both the apical-basal orientation of the mitotic spindle and the basal localisation of the protein determinants Numb and Prospero during mitosis [9].
• A protein complex containing Inscuteable and the Galpha-binding protein Pins orients asymmetric cell divisions in Drosophila [9].

References