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The Journal of Neuroscience, February 15, 1998, 18(4):1383-1392

Differential Regional Expression and Ultrastructural Localization of -Actinin-2, a Putative NMDA Receptor-Anchoring Protein, in Rat Brain

Michael Wyszynski¹, Viktor Kharazia², Roopal Shanghvi¹, Anuradha Rao³, Alan H. Beggs⁴, Ann Marie Craig³, Richard Weinberg² and Morgan Sheng¹

¹ Howard Hughes Medical Institute and Department of Neurobiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, ² Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, ³ Department of Cell and Structural Biology, University of Illinois, Urbana-Champaign, Illinois 61801, and ⁴ Genetics Division, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115

Fast chemical neurotransmission is dependent on ionotropic receptors that are concentrated and immobilized at specific postsynaptic sites. The mechanisms of receptor clustering and anchoring in neuronal synapses are poorly understood but presumably involve molecular linkage of membrane receptor proteins to the postsynaptic cytoskeleton. Recently the actin-binding protein -actinin-2 was shown to bind directly to the NMDA receptor subunits NR1 and NR2B (), suggesting that -actinin-2 may function to attach NMDA receptors to the actin cytoskeleton. Here we show that -actinin-2 is localized specifically in glutamatergic synapses in cultured hippocampal neurons. By immunogold electron microscopy, -actinin-2 is concentrated over the postsynaptic density (PSD) of numerous asymmetric synapses where it colocalizes with NR1 immunoreactivity. Thus -actinin-2 is appropriately positioned at the ultrastructural level to function as a postsynaptic-anchoring protein for NMDA receptors. -Actinin-2 is not, however, exclusively found at the PSD; immunogold labeling was also associated with filaments and the spine apparatus of dendritic spines and with microtubules in dendritic shafts. -Actinin-2 showed marked differential regional expression in rat brain. For instance, the protein is expressed at much higher levels in dentate gyrus than in area CA1 of the hippocampus. This differential regional expression implies that glutamatergic synapses in various parts of the brain differ with respect to their -actinin-2 content and thus, potentially, the extent of possible interaction between -actinin-2 and the NMDA receptor.

Key words: -actinin; NMDA receptor; GKAP; glutamatergic synapses; postsynaptic density; actin cytoskeleton

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Copyright © 1998 Society for Neuroscience  0270-6474/98/1841383-10$05.00/0

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