title: Synaptic glutamate receptor clustering in mice lacking the SH3 and GK domains of SAP97.
abstract: Postsynaptic targeting of the Drosophila tumour suppressor discs-large (Dlg) critically depends on its SH3 and GK domains. Here, we asked whether these domains are also involved in subcellular targeting of the mammalian Dlg homolog SAP97 and its interacting partners in CNS cortical neurons by analysing a recently described mouse mutant lacking the SH3 and GK domains of SAP97. Both wildtype and truncated SAP97 were predominantly expressed in perinuclear regions, in a pattern suggesting association with the endoplasmic reticulum. Weaker immunoreactivity was found in neurites colocalizing with both dendritic and axonal markers. As SAP97 has been implicated in the early intracellular processing of the glutamate receptor GluR1, we studied biochemical maturation and subcellular localization of GluR1 in the mutants. Both the glycosylation pattern and synaptic clustering of GluR1 were indistinguishable from wildtype mice. Synaptic clustering of the guanylate kinase domain interacting protein GKAP was also intact. Our data demonstrate that truncation of the SH3 and GK domains of SAP97 in mice does neither change its subcellular distribution nor does it disrupt synaptic structure or protein clustering, as opposed to severe missorting of the respective mutant Dlg protein in Drosophila.
authors.affiliation: Department of Physiology, University of California, San Francisco, CA 94143, USA.
authors.forename: Nikolaj
authors.initials: N
authors.lastname: Klöcker
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bunn
authors.forename: Eric
authors.initials: E
authors.lastname: Schnell
authors.forename: Georgina
authors.initials: G
authors.lastname: Caruana
authors.forename: Alan
authors.initials: A
authors.lastname: Bernstein
authors.forename: Roger A
authors.initials: RA
authors.lastname: Nicoll
authors.forename: David S
authors.initials: DS
authors.lastname: Bredt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002451:Cell Compartmentation / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D003712:Dendrites / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D000074288:Discs Large Homolog 1 Protein; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D051528:Guanylate Kinases; D007150:Immunohistochemistry; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000074288:Discs Large Homolog 1 Protein; D051528:Guanylate Kinases; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C000614189:Dlg1 protein, mouse; C104724:glutamate receptor ionotropic, AMPA 4; C104722:glutamate receptor ionotropic, AMPA 2