Regulation of Synapse Structure and Function by the Drosophila Tumor Suppressor Gene dlg

Budnik, Vivian; Koh, Young‐Sang; Guan, Bo; Hartmann, Beate; Hough, Colleen D.; Woods, Daniel F.; Gorczyca, Michael

doi:10.1016/s0896-6273(00)80196-8

Cited by 389 publications

(433 citation statements)

References 49 publications

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“…Indeed, Drosophila dlg has been shown to be able to function both cell-and non-cell-autonomously. For example, at dlg mutant neuromuscular junctions, a presynaptic cellspecific dlg transgene rescues the postsynaptic structural defect better than a postsynaptic cell-specific dlg transgene, suggesting that neurotransmitter release promoted by dlg inf luences postsynaptic cell phenotype (26).…”

Section: Discussionmentioning

confidence: 99%

Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter

Mahoney¹,

Sammut

Xavier

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

100

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Discs-large homolog 1 (DLGH1) is a mouse ortholog of the Drosophila discs-large (DLG) tumor suppressor protein, a founding member of the PDZ and MAGUK protein families. DLG proteins play important roles in regulating cell proliferation, epithelial cell polarity, and synapse formation and function. Here, we generated a null allele of Dlgh1 and studied its role in urogenital development. Dlgh1 ؊/؊ mice developed severe urinary tract abnormalities, including congenital hydronephrosis, which is the leading cause of renal failure in infants and children. DLGH1 is expressed in the developing ureter; in its absence, the stromal cells that normally lie between the urothelial and smooth muscle layers were missing. Moreover, in ureteric smooth muscle, the circular smooth muscle cells were misaligned in a longitudinal orientation. These abnormalities in the ureter led to severely impaired ureteric peristalsis. Similar smooth muscle defects are observed frequently in patients with ureteropelvic junction obstruction, a common form of hydronephrosis. Our results suggest that (i) besides its well documented role in regulating epithelial polarity, Dlgh1 also regulates smooth muscle orientation, and (ii) human DLG1 mutations may contribute to hereditary forms of hydronephrosis.SAP97 ͉ kidney ͉ postsynaptic density-95/discs-large/zonula occludens-1 ͉ urogenital ͉ sonic hedgehog

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Section: Discussionmentioning

confidence: 99%

Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter

Mahoney¹,

Sammut

Xavier

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

100

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“…In the nervous system, nTSGs are required both for the asymmetric division of neuroblasts and for the organization of the neuromuscular synapse (Budnik et al 1996;Ohshiro et al 2000;Peng et al 2000;Mathew et al 2002). However, they are by no means required for all events of cell polarization.…”

Section: Polaritymentioning

confidence: 99%

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Bilder¹

2004

Genes Dev.

517

510

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Mammalian epithelial tumors lose polarity as they progress toward malignancy, but whether polarity loss might causally contribute to cancer has remained unclear. In Drosophila, mutations in the "neoplastic tumor suppressor genes" (nTSGs) scribble, discs-large, and lethal giant larvae disrupt polarity of epithelia and neuroblasts, and simultaneously induce extensive overproliferation of these cells, which exhibit malignant-like characteristics. Herein I review what is known about the role of the fly nTSGs in controlling cell polarity and cell proliferation. Incorporating data from mammalian studies, I consider how polarity and proliferation can be coupled, and how disruption of polarity could promote cancer.

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“…The following GAL4 lines were used in this study: BG57-GAL4 (Budnik et al, 1996), MHC-GeneSwitch-GAL4 (MHC-GS-GAL4 ) (Osterwalder et al, 2001), and C155-GAL4 (Lin and Goodman, 1994).…”

Section: Uas-arp3mentioning

confidence: 99%

dCIP4 (Drosophila Cdc42-Interacting Protein 4) Restrains Synaptic Growth by Inhibiting the Secretion of the Retrograde Glass Bottom Boat Signal

Nahm

Kim²,

Paik³

et al. 2010

Journal of Neuroscience

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The bone morphogenetic protein (BMP) ligand Glass bottom boat (Gbb) acts as a retrograde growth signal at the Drosophila neuromuscular junction (NMJ). Endocytic regulation of presynaptic BMP receptors has been proposed to attenuate retrograde BMP signaling. However, it remains unknown whether the Gbb signal is also regulated by postsynaptic mechanisms. Here, we provide evidence that Drosophila Cdc42-interacting protein 4 (dCIP4) functions postsynaptically to inhibit synaptic growth. dCIP4 is localized postsynaptically at NMJs. dcip4 mutations lead to synaptic overgrowth and increased presynaptic phosphorylated mothers against decapentaplegic (Mad) levels, and these defects are rescued by muscle-specific expression of dCIP4. Biochemical and genetic analyses demonstrate that dCIP4 acts downstream of Cdc42 to activate the postsynaptic Wsp-Arp2/3 pathway. We also show that BMP signaling is necessary for synaptic overgrowth in larvae lacking postsynaptic dcip4 or wsp. Finally, dCIP4 and Wsp inhibit Gbb secretion. Thus, we propose that dCIP4 restrains synaptic growth by inhibiting postsynaptic Gbb secretion through the Wsp-Arp2/3 pathway.

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Regulation of Synapse Structure and Function by the Drosophila Tumor Suppressor Gene dlg

Cited by 389 publications

References 49 publications

Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter

Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

dCIP4 (Drosophila Cdc42-Interacting Protein 4) Restrains Synaptic Growth by Inhibiting the Secretion of the Retrograde Glass Bottom Boat Signal

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