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

Mahoney, Zhen X.; Sammut, BÃ©nÃ©dicte; Xavier, Ramnik J.; Cunningham, Jeanette M.; Go, Gloriosa; Brim, Karry; Stappenbeck, Thaddeus S.; Miner, Jeffrey H.; Swat, Wojciech

doi:10.1073/pnas.0609326103

Cited by 100 publications

(105 citation statements)

References 35 publications

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“…Nevertheless, in mammals like in Drosophila, spermatogenesis depends on interactions between supportive Sertoli cells and germ cells [42]. Moreover, inactivation of the Dlgh-1 gene in mice produces various abnormalities in their renal and urogenital organs with hypoplasia of kidneys and ureters, and absence of vagina and seminal vesicle [43,44]. Generation of mice conditional for the expression of homologs of the Drosophila dlg would provide a suitable system for investigating their functions during mammalian gonadogenesis.…”

Section: Discussionmentioning

confidence: 99%

discs large regulates somatic cyst cell survival and expansion in Drosophila testis

Papagiannouli

Mechler

2009

Cell Res

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Gonad development requires a coordinated soma-germline interaction that ensures renewal and differentiation of germline and somatic stem cells to ultimately produce mature gametes. The Drosophila tumour suppressor gene discs large (dlg) encodes a septate junction protein functioning during epithelial polarization, asymmetric neuroblast division, and formation of neuromuscular junctions. Here, we report the role of dlg in testis development and its critical function in somatic cyst cells (SCCs). In these cells dlg is primarily required for their survival and expansion, and contributes to spermatocyte cyst differentiation. Cell death primarily occurred in SCCs at the end of spermatogonial amplification at a time when Dlg becomes restricted in wild-type (wt) testes to the distal somatic cells capping the growing spermatocyte cysts. RNAi depletion of dlg transcripts in early SCCs fully prevented testis development, whereas depletion in late SCCs resulted in a breakdown of spermatocyte cyst structure and germ cell individualization. Specific dlg expression in SCCs resulted in developmental rescue of dlg mutant testes, whereas its expression in germ cells exerted no such effect. dlg overexpression in wt testes led to spermatocyte cyst expansion at the expense of spermatogonial cysts. Our data demonstrate that dlg is essentially required in SCCs for their survival, expansion, and differentiation, and for the encapsulation of the germline cells.

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Section: Discussionmentioning

confidence: 99%

discs large regulates somatic cyst cell survival and expansion in Drosophila testis

Papagiannouli

Mechler

2009

Cell Res

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“…In Dlgh1 fl/fl mice, exon 4 of the Dlgh1 gene is flanked upstream and downstream by loxP sites (33). Recombination that these sites produces a truncated transcript that is not translated into a functional protein (34). Mice homozygous for this genotype were bred with nestin-Cre transgenic mice.…”

Section: Methodsmentioning

confidence: 99%

The role of SAP97 in synaptic glutamate receptor dynamics

Howard

Elias

et al. 2010

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

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Proteins of the PSD-95-like membrane-associated guanylate kinase (PSD-MAGUK) family are vital for trafficking AMPA receptors (AMPARs) to synapses, a process necessary for both basal synaptic transmission and forms of synaptic plasticity. Synapse-associated protein 97 (SAP97) exhibits protein interactions, such as direct interaction with the GluA1 AMPAR subunit, and subcellular localization (synaptic, perisynaptic, and dendritic) unique within this protein family. Due in part to the lethality of the germline knockout of SAP97, this protein's role in synaptic transmission and plasticity is poorly understood. We found that overexpression of SAP97 during early development traffics AMPARs and NMDA receptors (NMDARs) to synapses, and that SAP97 rescues the deficits in AMPAR currents normally seen in PSD-93/-95 double-knockout neurons. Mature neurons that have experienced the overexpression of SAP97 throughout development exhibit enhanced AMPAR and NMDAR currents, as well as faster NMDAR current decay kinetics. In loss-of-function experiments using conditional SAP97 gene deletion, we recorded no deficits in glutamatergic transmission or long-term potentiation. These results support the hypothesis that SAP97 is part of the machinery that traffics glutamate receptors and compensates for other PSD-MAGUKs in knockout mouse models. However, due to functional redundancy, other PSD-MAGUKs can presumably compensate when SAP97 is conditionally deleted during development.AMPA | hippocampus | membrane-associated guanylate kinase | NMDA | postsynaptic density | synaptic transmission | synaptic development T he excitatory postsynaptic density (PSD) stabilizes AMPA receptors (AMPARs) and NMDA receptors (NMDARs) opposed to presynaptic terminals, providing a foundation for synaptic transmission and bidirectional receptor trafficking during plasticity. A major PSD component is the PSD-95-like membrane-associated guanylate kinase (PSD-MAGUK) protein family, which includes PSD-95/SAP90, PSD-93/Chapsyn-110, synapse-associated protein (SAP) 102, and SAP97, the mammalian homolog of Drosophila tumor-suppressor discs large (Dlg1) (1, 2), All PSD-MAGUKs contain protein-protein interaction motifs, most notably three PSD95/Dlg/ZO-1 (PDZ) domains (3-5), which provide a scaffold for synaptic protein complexes. PSD-95 and PSD-93 play critical roles in AMPAR trafficking at mature synapses, whereas SAP102 is most important during synaptogenesis (6-13). PSD-MAGUKs also are important for localizing NMDA receptors, especially during synapse development (14-17).Unlike other PSD-MAGUKs, SAP97β, the major isoform of the protein (also known as DLGH1; encoded by Dlgh1), is expressed at presynaptic and postsynaptic sites (2, 18) and perisynaptically in dendritic spines (19). SAP97β directly binds to AMPAR GluA1 subunits (20-23). Because SAP97 has been resistant to RNAi in our hands (but see 10) and germline KO causes lethal feeding deficits in neonatal mice (24), SAP97's synaptic function is uncertain and is based primarily on dissociated neuronal culture stu...

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“…Either sense or antisense RNA probes were generated using the Roche DIG RNA labeling kit (Roche Applied Science). RNA probes for c-Ret, Pax2, Wnt11, Gdnf, (19), and Gata3 (20) were also generated and used in the analyses. Images were acquired on a Leica dissecting microscope (model MZ9 5 ) using a Zeiss Axiocam and Axiovision software.…”

Section: Methodsmentioning

confidence: 99%

The Leucine Zipper Putative Tumor Suppressor 2 Protein LZTS2 Regulates Kidney Development

Peng

Clark

Luong

et al. 2011

Journal of Biological Chemistry

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Background:The LZTS2 is a novel ␤-catenin-interacting protein, and its role in development and tumorigenesis is unknown. Results: Lzts2 KO mice show severe kidney and urinary tract developmental defects, including renal/ureteral duplication, hydroureter, and hydronephrosis. Conclusion: LZTS2 plays a critical role in kidney and urinary tract development. Significance: A novel mechanism by which LZTS2 regulates ␤-catenin mediated nephrogenesis is implicated.

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

Cited by 100 publications

References 35 publications

discs large regulates somatic cyst cell survival and expansion in Drosophila testis

discs large regulates somatic cyst cell survival and expansion in Drosophila testis

The role of SAP97 in synaptic glutamate receptor dynamics

The Leucine Zipper Putative Tumor Suppressor 2 Protein LZTS2 Regulates Kidney Development

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