Glutamate receptors localize postsynaptically at neuromuscular junctions in mice.

Dlg (Discs Large) is a multidomain protein that interacts with glutamate receptors and potassium channels at Drosophila neuromuscular junctions (NMJs) and at mammalian central nervous system synapses. Dlg also localizes postsynaptically at cholinergic mammalian NMJs. We show here that alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) receptor subunits, together with glutamate, are present at the mammalian NMJ.

Truncated CASK does not alter skeletal muscle or protein interactors.

CASK (Ca2+, calmodulin-associated serine/threonine kinase) is an essential mammalian cell junction protein and is also crucial at Drosophila neuromuscular synapses. We have shown that CASK is present in mammalian skeletal muscle at the postsynaptic membrane of the neuromuscular junction. CASK interacts biochemically with channels at central synapses, and studies in cultured cells have led to proposed functions for CASK.

CASK localizes to nuclei in developing skeletal muscle and motor neuron culture models and is agrin-independent.

Membrane-associated guanylate kinases (MAGUKs) are cytoplasmic multi-domain proteins that serve as scaffold proteins at cell junctions and synapses. Calmodulin-associated serine/threonine kinase (CASK) stabilizes the integrity of synapses in the brain. Additionally, CASK is capable of acting as a transcriptional co-activator and localizes to neuronal nuclei in the developing brain.

Claudin-5 localizes to the lateral membranes of cardiomyocytes and is altered in utrophin/dystrophin-deficient cardiomyopathic mice.

Remodeling of adherens junction, gap junction, and desmosomal proteins at the intercalated discs of cardiomyocytes in heart characterizes several animal models of cardiomyopathy, especially dilated cardiac myopathy (DCM). In this study, we show that the tight junction protein, claudin-5, is present in cardiac muscle and localizes to the lateral membranes of cardiomyocytes in normal mice. We further examined claudin-5 in utrophin/dystrophin-deficient (double knockout, dko) mice, a mouse model of muscular dystrophy with cardiomyopathy, and found that claudin-5 mRNA and protein levels are decreased in dko hearts as compared with normal.

CASK and Dlg form a PDZ protein complex at the mammalian neuromuscular junction.

Membrane-associated guanylate kinases (MAGUKs) are modular adapter proteins that serve as scaffolding molecules and anchor channels and receptors via their PDZ (PSD-95, Dlg, Zo-1) domains. Calcium, calmodulin-associated serine/threonine kinase (CASK) is a MAGUK that is critical at synapses in the central nervous system and at cell-cell junctions because of its interactions with channels, receptors, and structural proteins. We show via confocal microscopy that CASK and another MAGUK, Discs Large (Dlg), are present at the mammalian neuromuscular junction in skeletal muscle.