Cell polarity plays an important role in tissue morphogenesis; however, the mechanisms of polarity and their role in mammalian development are still poorly understood. We show here that membrane-associated guanylate kinase protein Dlg5 is required for proper branching morphogenesis and progenitor differentiation in mammalian lung. We found that during lung development Dlg5 functions as an apical-basal polarity protein, which is necessary for the apical maintenance of atypical protein kinase C (aPKC). These results identify Dlg5 as a regulator of apical polarity complexes and uncover the critical function of Dlg5 in branching morphogenesis and differentiation of lung progenitor cells.
"Although there does not appear to be any examples of DLG5 in the direct regulation of GPCRs, DLG5 has been implicated in regulating synaptogenesis by enhancing the membrane localization of the transmembrane protein N-cadherin (Wang et al., 2014). DLG5 has also been demonstrated to scaffold atypical protein kinase C (PKC) isoforms, and this provides a mechanism by which DLG5 contributes to the regulation of GPCR-mediated signaling (Nechiporuk et al., 2013). "
[Show abstract][Hide abstract] ABSTRACT: G protein-coupled receptors (GPCRs) contribute to the regulation of every aspect of human physiology and are the therapeutic targets for the treatment of numerous diseases. As a consequence, understanding the myriad of mechanisms controlling GPCR signalling and trafficking is essential for the development of new pharmacological strategies for the treatment of human pathologies. Of the many GPCR-interacting proteins (GIPs), PDZ domain-containing proteins appear most abundant and have similarly been implicated in disease mechanisms. PDZ proteins play an important role at regulating receptor and channel protein localization of synapses and tight junctions and function to scaffold intracellular signalling protein complexes. In the current study, we review the known functional interactions between PDZ domain-containing proteins and GPCRs, and provide insight into the potential mechanisms of action. These PDZ domain-containing proteins include the membrane-associated guanylate-like kinases (MAGUKs) (PSD-95, SAP97, PSD-93, SAP102, DLG5, CARMA3, MPP3, CASK, MAGI-1, MAGI-2, MAGI-3), NHERF proteins (NHERF1, NHERF2, PDZK1, PDZK2), Golgi-associated PDZ proteins (GIPC and CAL), PDZ-GEFs (PDZ-GEF1 and PDZ-GEF2), RGS-Homology-RhoGEFs (PDZ-RhoGEF and LARG), RGS3 and RGS12, spinophilin and neurabin-1, Shank proteins (Shank1, Shank2, Shank3), Par3 and Par6, MUPP1, Tamalin, nNOS, PICK1, and SNX27.
The American Society for Pharmacology and Experimental Therapeutics.
"ownloaded from ability to generate Gli repressor primarily from proteo - lytic processing of Gli3 in a Hh - regulated manner thus suffices to supply a substantial proportion of the Hh - mediated patterning activity required for embryonic de - velopment . It is worth noting in this context that Dlg5 À / À animals display defects in lung branching ( Nechiporuk et al . 2013 ) very much like those associated with genetic defects in Hh signaling ( Bellusci et al . 1997 ; Pepicelli et al . 1998 ; Miller et al . 2004 ) . In addition , Dlg5 single - nucle - otide polymorphisms ( SNPs ) have been identified in numerous families of European descent with inflamma - tory bowel disease ( IBD ) ( Friedrichs and Stoll"
"ZO1 interacts with ZO2 and ZO3 via their PDZ2 domains to form a tight junctional complex. DLG5 participates in regulation of cell polarity by promoting the apical localization of aPKC 31. It has been found that aPKC and ZO1 are mislocalized, while PAR3 and remains apically localized in DLG5 knockout mice 22, 31. "
[Show abstract][Hide abstract] ABSTRACT: Failure in establishment and maintenance of epithelial cell polarity contributes to tumorigenesis. Loss of expression and function of cell polarity proteins is directly related to epithelial cell polarity maintenance. The polarity protein discs large homolog 5 (DLG5) belongs to a family of molecular scaffolding proteins called Membrane Associated Guanylate Kinases (MAGUKs). As the other family members, DLG5 contains the multi-PDZ, SH3 and GUK domains. DLG5 has evolved in the same manner as DLG1 and ZO1, two well-studied MAGUKs proteins. Just like DLG1 and ZO1, DLG5 plays a role in cell migration, cell adhesion, precursor cell division, cell proliferation, epithelial cell polarity maintenance, and transmission of extracellular signals to the membrane and cytoskeleton. Since the roles of DLG5 in inflammatory bowel disease (IBD) and Crohn's disease (CD) have been reviewed, here, our review focuses on the roles of DLG5 in epithelial cell polarity maintenance and cancer development.
International journal of biological sciences 05/2014; 10(5):543-546. DOI:10.7150/ijbs.8888 · 4.51 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.