Research article summary (published 19 Sep 2000):

Synaptic targeting and localization of discs-large is a stepwise process controlled by different domains of the protein.

Full Abstract

BACKGROUND: Membrane-associated guanylate kinases (MAGUKs) assemble ion channels, cell-adhesion molecules and components of second messenger cascades into synapses, and are therefore potentially important for co-ordinating synaptic strength and structure. Here, we have examined the targeting of the Drosophila MAGUK Discs-large (DLG) to larval neuromuscular junctions. RESULTS: During development, DLG was first found associated with the muscle subcortical compartment and plasma membrane, and later was recruited to the postsynaptic membrane. Using a transgenic approach, we studied how mutations in various domains of the DLGprotein affect DLG targeting. Deletion of the HOOK region-the region between the Src homology 3 (SH3) domain and the guanylate-kinase-like (GUK) domain-prevented association of DLG with the subcortical network and rendered the protein largely diffuse. Loss of the first two PDZ domains led to the formation of large clusters throughout the plasma membrane, with scant targeting to the neuromuscular junction. Proper trafficking of DLG missing the GUK domain depended on the presence of endogenous DLG. CONCLUSIONS: Postsynaptic targeting of DLG requires a HOOK-dependent association with extrasynaptic compartments, and interactions mediated by the first two PDZ domains. The GUK domain routes DLG between compartments, possibly by interacting with recently identified cytoskeletal-binding partners.

Author information

Author/s: Thomas, U (U); Ebitsch, S (S); Gorczyca, M (M); Koh, Y H (YH); Hough, C D (CD); Woods, D (D); Gundelfinger, E D (ED); Budnik, V (V);

Affiliation: Department of Biology, University of Massachusetts, Amherst, 01003, Massachusetts, USA.

Grants: R01 NS30072 (Agency:NINDS NIH HHS) ; R01 NS37061 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

Journal: Current biology : CB (Curr Biol), published in ENGLAND. (Language: eng)

Reference: 2000-Sep; vol 10 (issue 18) : pp 1108-17

Dates: Created 2000/10/25; Completed 2000/12/07; Revised 2007/11/14;

PMID: 10996791, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Animals, Genetically Modified Cell Membrane - metabolism Drosophila - genetics; metabolism Drosophila Proteins Guanylate Kinase Insect Proteins - chemistry; genetics; metabolism Membrane Proteins - immunology; metabolism Muscles - metabolism

Muscles - metabolism Neuromuscular Junction Nucleoside-Phosphate Kinase - chemistry; genetics; immunology; metabolism Protein Structure, Tertiary Protein Transport Recombinant Fusion Proteins - immunology; metabolism Sequence Deletion - genetics Synapses - metabolism Tumor Suppressor Proteins

Associated Chemicals: Drosophila Proteins (0) ; Insect Proteins (0) ; Membrane Proteins (0) ; Recombinant Fusion Proteins (0) ; Tumor Suppressor Proteins (0) ; discs large 1 protein, Drosophila (143513-41-1) ; Nucleoside-Phosphate Kinase (EC 2.7.4.4) ; Guanylate Kinase (EC 2.7.4.8)

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