No abstract

Chapsyn-110, a novel membrane-associated putative guanylate kinase (MAGUK) that binds directly to N-methyl-D-aspartate (NMDA) receptor and Shaker K+ channel subunits, is 70%-80% identical to, and shares an identical domain organization with, PSD-95/SAP90 and SAP97. In rat brain, chapsyn-110 protein shows a somatodendritic expression pattern that overlaps partly with PSD-95 but that contrasts with the axonal distribution of SAP97. Chapsyn-110 associates tightly with the postsynaptic density in brain, and mediates the clustering of both NMDA receptors and K+ channels in heterologous cells. Indeed, chapsyn-110 and PSD-95 can heteromultimerize with each other and are recruited into the same NMDA receptor and K+ channel clusters. Thus, chapsyn-110 and PSD-95 may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signalling proteins.

During early embryogenesis in Drosophila melanogaster, extensive vesicle transport occurs to build cell boundaries for 6,000 nuclei. Here we show that this important process depends on a functional complex formed between the tumour suppressor and adaptor protein Discs-Large (Dlg) 1 and the integral membrane protein Strabismus (Stbm)/Van Gogh (Vang) 2,3 . In support of this idea, embryos with mutations in either dlg or stbm displayed severe defects in plasma membrane formation. Conversely, overexpression of Dlg and Stbm synergistically induced excessive plasma membrane formation. In addition, ectopic co-expression of Stbm (which associated with postGolgi vesicles) and the mammalian Dlg homologue SAP97/hDlg 4,5 promoted translocation of SAP97 from the cytoplasm to both post-Golgi vesicles and the plasma membrane. This effect was dependent on the interaction between Stbm and SAP97. These findings suggest that the Dlg-Stbm complex recruits membrane-associated proteins and lipids from internal membranes to sites of new plasma membrane formation.Formation of new plasma membranes is dependent on the delivery of post-Golgi vesicles to a pre-existing plasma membrane. An excellent model system to study this process is the cellularization that occurs during early Drosophila embryogenesis. During cellularization, the embryonic plasma membrane must rapidly grow inwards to segregate thousands of nuclei, generated by synchronized cycles of nuclear division without cytokinesis, into individual cells 6 . This process occurs through addition of post-Golgi vesicles to defined regions of lengthening plasma membranes and may be required for establishing proper cell polarity 7 . The Dlg tumour suppressor is essential both for establishing proper cell polarity and for assembling multiprotein complexes at specialized cell-cell junctions 8 . Accumulating evidence also indicates that Dlg associates with its targets at intracellular membrane sites before accumulation at the plasma membrane 9-12 . The integral membrane protein Stbm, however, is a regulator of planar tissue polarity in the fly 2,3 , and mouse Loop-tail (Lp) and zebrafish trilobite mutants that also have mutations in stbm homologues display defects in gastrulation and neurogenesis 13,14 .Here,we report that Dlg binds to Stbm and that this complex is required for formation of new plasma membranes during cellularization. Note: Supplementary Information is available on the Nature Cell Biology website. COMPETING FINANCIAL INTERESTSThe authors declare that they have no competing financial interests. We identified Stbm as a binding partner of Dlg using the first and second Dlg PDZ domains (Dlg-PDZ1-2; Fig. 1a) as bait in the yeast two-hybrid system. Stbm contains four putative transmembrane domains and a consensus PDZ-domain-binding motif (PBM) at its extreme carboxyl terminus (Fig. 1a) 2 . In glutathione S -transferase (GST) pull-down assays, the 17 C-terminal residues of Stbm (GST-Stbm PBM ) were sufficient to mediate binding to Dlg-PDZ1-2 (see Supplementary Information,...

ADAMTS (a disintegrin and metalloproteases with thrombospondin motif) family consists of secreted proteases, and is shown to cleave extracellular matrix proteins. Their malfunctions result in cancers and disorders in connective tissues. We report here that a Drosophila ADAMTS named Sol narae (Sona) promotes Wnt/Wingless (Wg) signaling. sona loss-of-function mutants are lethal and rare escapers had malformed appendages, indicating that sona is essential for fly development and survival. sona exhibited positive genetic interaction with wntless (wls) that encodes a cargo protein for Wg. Loss of sona decreased the level of extracellular Wg, and also reduced the expression level of Wg effector proteins such as Senseless (Sens), Distalless (Dll) and Vestigial (Vg). Sona and Wg colocalized in Golgi and endosomal vesicles, and were in the same protein complex. Furthermore, co-expression of Wg and Sona generated ectopic wing margin bristles. This study suggests that Sona is involved in Wg signaling by regulating the level of extracellular Wg.

Wolbachia pipientis are intracellular symbiotic bacteria extremely common in various organisms including Drosophila melanogaster, and are known for their ability to induce changes in host reproduction. These bacteria are present in astral microtubule-associated vesicular structures in host cytoplasm, but little is known about the identity of these vesicles. We report here that Wolbachia are restricted only to a group of Golgi-related vesicles concentrated near the site of membrane biogenesis and minus-ends of microtubules. The Wolbachia vesicles were significantly mislocalized in mutant embryos defective in cell/planar polarity genes suggesting that cell/tissue polarity genes are required for apical localization of these Golgi-related vesicles. Furthermore, two of the polarity proteins, Van Gogh/Strabismus and Scribble, appeared to be present in these Golgi-related vesicles. Thus, establishment of polarity may be closely linked to the precise insertion of Golgi vesicles into the new membrane addition site.