6mye
Crystal structure of human Scribble PDZ1 domain in complex with internal PDZ binding motif of Src homology 3 domain-containing guanine nucleotide exchange factor (SGEF)
Structural highlights
DiseaseSCRIB_HUMAN The disease is caused by mutations affecting the gene represented in this entry. FunctionSCRIB_HUMAN Scaffold protein involved in different aspects of polarized cells differentiation regulating epithelial and neuronal morphogenesis. Most probably functions in the establishment of apico-basal cell polarity. May function in cell proliferation regulating progression from G1 to S phase and as a positive regulator of apoptosis for instance during acinar morphogenesis of the mammary epithelium. May also function in cell migration and adhesion and hence regulate cell invasion through MAPK signaling. May play a role in exocytosis and in the targeting synaptic vesicles to synapses. Functions as an activator of Rac GTPase activity.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedThe canonical Scribble polarity complex is implicated in regulation of epithelial junctions and apical polarity. Here, we show that SGEF, a RhoG-specific GEF, forms a ternary complex with Scribble and Dlg1, two members of the Scribble complex. SGEF targets to apical junctions in a Scribble-dependent fashion and functions in the regulation of actomyosin-based contractility and barrier function at tight junctions as well as E-cadherin-mediated formation of adherens junctions. Surprisingly, SGEF does not control the establishment of polarity. However, in 3D cysts, SGEF regulates the formation of a single open lumen. Interestingly, SGEF's nucleotide exchange activity regulates the formation and maintenance of adherens junctions, and in cysts the number of lumens formed, whereas SGEF's scaffolding activity is critical for regulation of actomyosin contractility and lumen opening. We propose that SGEF plays a key role in coordinating junctional assembly and actomyosin contractility by bringing together Scribble and Dlg1 and targeting RhoG activation to cell-cell junctions. SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility.,Awadia S, Huq F, Arnold TR, Goicoechea SM, Sun YJ, Hou T, Kreider-Letterman G, Massimi P, Banks L, Fuentes EJ, Miller AL, Garcia-Mata R J Cell Biol. 2019 Jun 27. pii: jcb.201811114. doi: 10.1083/jcb.201811114. PMID:31248911[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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