» Articles » PMID: 22084305

The Rap1-Rgl-Ral Signaling Network Regulates Neuroblast Cortical Polarity and Spindle Orientation

Overview
Journal J Cell Biol
Specialty Cell Biology
Date 2011 Nov 16
PMID 22084305
Citations 23
Authors
Affiliations
Soon will be listed here.
Abstract

A crucial first step in asymmetric cell division is to establish an axis of cell polarity along which the mitotic spindle aligns. Drosophila melanogaster neural stem cells, called neuroblasts (NBs), divide asymmetrically through intrinsic polarity cues, which regulate spindle orientation and cortical polarity. In this paper, we show that the Ras-like small guanosine triphosphatase Rap1 signals through the Ral guanine nucleotide exchange factor Rgl and the PDZ protein Canoe (Cno; AF-6/Afadin in vertebrates) to modulate the NB division axis and its apicobasal cortical polarity. Rap1 is slightly enriched at the apical pole of metaphase/anaphase NBs and was found in a complex with atypical protein kinase C and Par6 in vivo. Loss of function and gain of function of Rap1, Rgl, and Ral proteins disrupt the mitotic axis orientation, the localization of Cno and Mushroom body defect, and the localization of cell fate determinants. We propose that the Rap1-Rgl-Ral signaling network is a novel mechanism that cooperates with other intrinsic polarity cues to modulate asymmetric NB division.

Citing Articles

p53 tumor suppressor directly activates conserved asymmetric stem cell division regulators.

Manzanero-Ortiz S, Franco M, Laxmeesha M, Carmena A iScience. 2024; 27(11):111118.

PMID: 39524346 PMC: 11546965. DOI: 10.1016/j.isci.2024.111118.


Rap1 regulates lumen continuity via Afadin in renal epithelia.

Hiremath C, Gao L, Geshow K, Patterson Q, Barlow H, Cleaver O Dev Biol. 2023; 501:20-27.

PMID: 37276970 PMC: 10460627. DOI: 10.1016/j.ydbio.2023.05.003.


Parallel Rap1>RalGEF>Ral and Ras signals sculpt the C. elegans nervous system.

Mardick J, Rasmussen N, Wightman B, Reiner D Dev Biol. 2021; 477:37-48.

PMID: 33991533 PMC: 8277711. DOI: 10.1016/j.ydbio.2021.05.004.


A Genetic Screen for Human Genes Suppressing FUS Induced Toxicity in Yeast.

Hayden E, Chen S, Chumley A, Xia C, Zhong Q, Ju S G3 (Bethesda). 2020; 10(6):1843-1852.

PMID: 32276960 PMC: 7263679. DOI: 10.1534/g3.120.401164.


De novo mutations in the GTP/GDP-binding region of RALA, a RAS-like small GTPase, cause intellectual disability and developmental delay.

Hiatt S, Neu M, Ramaker R, Hardigan A, Prokop J, Hancarova M PLoS Genet. 2018; 14(11):e1007671.

PMID: 30500825 PMC: 6291162. DOI: 10.1371/journal.pgen.1007671.


References
1.
Parmentier M, Woods D, Greig S, Phan P, Radovic A, Bryant P . Rapsynoid/partner of inscuteable controls asymmetric division of larval neuroblasts in Drosophila. J Neurosci. 2000; 20(14):RC84. PMC: 6772325. View

2.
Shen C, Jan L, Jan Y . Miranda is required for the asymmetric localization of Prospero during mitosis in Drosophila. Cell. 1997; 90(3):449-58. DOI: 10.1016/s0092-8674(00)80505-x. View

3.
Frasch M, Hoey T, Rushlow C, Doyle H, Levine M . Characterization and localization of the even-skipped protein of Drosophila. EMBO J. 1987; 6(3):749-59. PMC: 553460. DOI: 10.1002/j.1460-2075.1987.tb04817.x. View

4.
Johnston C, Hirono K, Prehoda K, Doe C . Identification of an Aurora-A/PinsLINKER/Dlg spindle orientation pathway using induced cell polarity in S2 cells. Cell. 2009; 138(6):1150-63. PMC: 2789599. DOI: 10.1016/j.cell.2009.07.041. View

5.
Spana E, Doe C . The prospero transcription factor is asymmetrically localized to the cell cortex during neuroblast mitosis in Drosophila. Development. 1995; 121(10):3187-95. DOI: 10.1242/dev.121.10.3187. View