The Drosophila RGS protein Loco is required for dorsal/ventral axis formation of the egg and embryo, and nurse cell dumping

Pathirana, Stephen; Zhao, Debiao; Bownes, Mary

doi:10.1016/s0925-4773(01)00557-3

Cited by 17 publications

(24 citation statements)

References 42 publications

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“…Here we show that locomotion defects (loco), a gene previously shown to be required for glial cell differentiation and dorsal-ventral patterning (Granderath et al 1999;Pathirana et al 2001), encodes a novel component of the NB apical complex that exhibits both guanine nucleotide dissociation inhibitor (GDI) and GTPase-activating protein (GAP) activities for G␣i. Loco interacts with GDP-G␣i through its GoLoco motif (Siderovski et al 1999) and forms a complex with G␣i in vivo.…”

mentioning

confidence: 70%

Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions

Yu¹,

Wang²,

Qian³

et al. 2005

Genes Dev.

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Heterotrimeric G proteins mediate asymmetric division of Drosophila neuroblasts. Free G␤␥ appears to be crucial for the generation of an asymmetric mitotic spindle and consequently daughter cells of distinct size. However, how G␤␥ is released from the inactive heterotrimer remains unclear. Here we show that Locomotion defects (Loco) interacts and colocalizes with G␣i and, through its GoLoco motif, acts as a guanine nucleotide dissociation inhibitor (GDI) for G␣i. Simultaneous removal of the two GoLoco motif proteins, Loco and Pins, results in defects that are essentially indistinguishable from those observed in G␤13F or G␥1 mutants, suggesting that Loco and Pins act synergistically to release free G␤␥ in neuroblasts. Furthermore, the RGS domain of Loco can also accelerate the GTPase activity of G␣i to regulate the equilibrium between the GDP-and the GTP-bound forms of G␣i. Thus, Loco can potentially regulate heterotrimeric G-protein signaling via two distinct modes of action during Drosophila neuroblast asymmetric divisions. Asymmetric cell division is a universal mechanism used to generate cellular diversity during development. The Drosophila embryonic central nervous system (CNS) derives largely from neural progenitors called neuroblasts (NBs). NBs delaminate from the neuroectoderm and undergo asymmetric cell division along the apical/basal axis to give rise to two daughters of distinct fate and size. The larger apical daughter cell retains a NB identity and undergoes repeated asymmetric divisions, whereas the smaller basal daughter differentiates into a ganglion mother cell (GMC) that divides only once to generate two neurons/glia (Campos-Ortega 1997). Three wellcharacterized features of the NB asymmetric divisions (Jan and Jan 2001; Knoblich 2001; Wodarz and Huttner 2003) are (1) asymmetric localization and segregation of cell fate determinants and their adaptor proteins Numb/ Partner of Numb (Pon), Prospero (Pros)/Miranda (Mira) into the basal GMC; (2) reorientation of the mitotic spindle along the apical/basal axis at metaphase; (3) generation of an apically biased asymmetric mitotic spindle (Kaltschmidt et al. 2000;Kaltschmidt and Brand 2002) and the displacement of the spindle toward the basal cortex during ana/telophase as well as asymmetric formation of astral microtubules (MTs) (Giansanti et al. 2001), which lead to the generation of two unequal-sized daughter cells.These features of the NB asymmetric division are controlled by an apically localized complex of proteins that include the Drosophila homologs (Doe and Bowerman 2001) of the conserved Par3 (Bazooka, Baz)/Par6 (DmPar6)/aPKC (DaPKC) protein cassette first identified in Caenorhabditis elegans (Kemphues 2000), the novel protein Inscuteable (Insc), G␣i, a subunit of heterotrimeric G proteins (Schaefer et al. 2001;Yu et al. 2003), and an evolutionarily conserved molecule, Partner of Insc (Pins) (Parmentier et al. 2000;Schaefer et al. 2000;Yu et al. 2000) that acts as a guanine nucleotide dissociation inhibitor (GDI) for G␣i. Loss of single member...

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confidence: 70%

Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions

Yu¹,

Wang²,

Qian³

et al. 2005

Genes Dev.

Self Cite

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“…Embryos lacking the loco gene display defects in glial cell differentiation and 936 WILLARD y KIMPLE y SIDEROVSKI consequently fail to hatch; rare adult escapers that do eclose show severe impairment of spontaneous locomotor activity (7). Loco was also found to be required for dorsal-ventral pattern formation in the Drosophila embryo (48). Yet despite this knowledge, no specific G-protein modulatory functions have been ascribed to Loco to help explain its particular role in these processes, nor has a GPCR been identified as having modulatory activity on Loco function.…”

Section: Loco and Rgs12mentioning

confidence: 99%

Return of the GDI: The GoLoco Motif in Cell Division

Willard

Kimple

Siderovski³

2004

Annu. Rev. Biochem.

188

201

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The GoLoco motif is a 19-amino-acid sequence with guanine nucleotide dissociation inhibitor activity against G-alpha subunits of the adenylyl-cyclase-inhibitory subclass. The GoLoco motif is present as an independent element within multidomain signaling regulators, such as Loco, RGS12, RGS14, and Rap1GAP, as well as in tandem arrays in proteins, such as AGS3, G18, LGN, Pcp-2/L7, and Partner of Inscuteable (Pins/Rapsynoid). Here we discuss the biochemical mechanisms of GoLoco motif action on G-alpha subunits in light of the recent crystal structure of G-alpha-i1 bound to the RGS14 GoLoco motif. Currently, there is sparse evidence for GoLoco motif regulation of canonical G-protein-coupled receptor signaling. Rather, studies of asymmetric cell division in Drosophila and Caenorhabditis elegans, as well as mammalian mitosis, implicate GoLoco proteins, such as Pins, GPR-1/GPR-2, LGN, and RGS14, in mitotic spindle organization and force generation. We discuss potential mechanisms by which GoLoco/Galpha complexes might modulate spindle dynamics.

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“…The signaling pathways, between the germline and the cells of the follicular epithelium that coordinate these processes, include the c-Jun-NH 2 -terminal kinase (JNK) pathway (Dequier et al, 2001;Dobens et al, 2001) and others that may involve GPCRs and cAMP signaling (Schneider and Spradling, 1997;Lannutti and Schneider, 2001;Pathirana et al, 2001). …”

Section: Nurse Cell Dumping and Apoptosismentioning

confidence: 99%

Vitellogenesis and Post-Vitellogenic Maturation of the Insect Ovarian Follicle

Swevers

2005

Comprehensive Molecular Insect Science

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The Drosophila RGS protein Loco is required for dorsal/ventral axis formation of the egg and embryo, and nurse cell dumping

Cited by 17 publications

References 42 publications

Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions

Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions

Return of the GDI: The GoLoco Motif in Cell Division

Vitellogenesis and Post-Vitellogenic Maturation of the Insect Ovarian Follicle

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