Heterotrimeric G Proteins Direct Two Modes of Asymmetric Cell Division in the Drosophila Nervous System

Abstract

In Drosophila, distinct mechanisms orient asymmetric cell division along the apical-basal axis in neuroblasts and along the anterior-posterior axis in sensory organ precursor (SOP) cells. Here, we show that heterotrimeric G proteins are essential for asymmetric cell division in both cell types. The G protein subunit G(alpha)i localizes apically in neuroblasts and anteriorly in SOP cells before and during mitosis. Interfering with G protein function by G(alpha)i overexpression or depletion of heterotrimeric G protein complexes causes defects in spindle orientation and asymmetric localization of determinants. G(alpha)i is colocalized and associated with Pins, a protein that induces the release of the betagamma subunit and might act as a receptor-independent G protein activator. Thus, asymmetric activation of heterotrimeric G proteins by a receptor-independent mechanism may orient asymmetric cell divisions in different cell types.

The β-Subunit of the Arabidopsis G Protein Negatively Regulates Auxin-Induced Cell Division and Affects Multiple Developmental Processes[W]

“…Although GPA1* is capable of constitutively activating its cognate effectors, it is unable to sequester G␤␥. This approach has been successful in distinguishing the predominant role of G protein subunits in Drosophila asymmetric cell division (Schaefer et al, 2001). The expression levels of two independent transformants of each G protein gene construct were quantitated, and the fold change over controls was determined (see supplemental data online).…”

“…(B) Expectations and observations based on the proposed hypotheses. Overexpression of native GPA1 is expected to reduce the free AGB1 pool, whereas the activated G␣, GPA1*, is unable to sequester AGB1 (Schaefer et al, 2001). (C) Favored model.…”

Insights into neural stem cell biology from flies

“…The apical complex (figure 3b) consists of the evolutionarily conserved Par proteins, Bazooka (Baz, Par3) and DmPar6, and the Drosophila homologue of the atypical protein kinase C, DaPKC (Kuchinke et al 1998;Schober et al 1999;Wodarz et al 1999;. In neuroblasts, the Baz/DmPar6/DaPKC complex binds through Baz to Inscuteable (Insc), and Insc, in turn, recruits Partner of Inscuteable (Pins) and Locomotion defective (Loco), which are two GDPdissociation inhibitors (GDIs) that interact with the heterotrimeric G protein subunit, Gai (Kraut & Campos-Ortega 1996;Parmentier et al 2000;Yu et al 2000Yu et al , 2003Yu et al , 2005Schaefer et al 2001).…”

Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts

“…NB asymmetric divisions are controlled by an apically localized complex of proteins that include the Drosophila homologs of the conserved Par3 (Bazooka, Baz)/Par6 (DmPar6)/atypical protein kinase C(DaPKC) proteins (Kuchinke et al 1998;Wodarz et al 2000;Petronczki and Knoblich 2001), Inscuteable (Insc) (Kraut et al 1996), and heterotrimeric G proteins G␣i (Schaefer et al 2001;Yu et al 2003) and their regulators Partner of Insc (Pins) (Yu et al 2000), Locomotion defects (Loco) , and a Pins-interacting protein mushroom body defective (Mud) (Bowman et al 2006;Izumi et al 2006;Siller et al 2006). The asymmetric localization of G␣i requires G␤ (Schaefer et al 2001;Yu et al 2003) and G␥ (Fuse et al 2003) and its membrane localization requires Ric-8 (Hampoelz et al 2005;Wang et al 2005). Basal protein localization and segregation are mediated by apical proteins through cortically localized tumor suppressors, Discs large (Dlg) and Lethal (2) giant larvae (Lgl) (Ohshiro et al 2000;Peng et al 2000).…”